Dissertations / Theses: 'Allergen immunotherapy'

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Dandrieux, Julien. "Influence of allergen-specific immunotherapy on allergen-specific IgG subclasses in dogs with atopic dermatitis /." [S.l.] : [s.n.], 2008. http://www.zb.unibe.ch/download/eldiss/08dandrieux_j.pdf.

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Gardner, Leanne M. (Leanne Margaret) 1977. "Modulation of the allergen-specific Tcell response." Monash University, Dept. of Pathology and Immunology, 2003. http://arrow.monash.edu.au/hdl/1959.1/5817.

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Beuraud, Chloé. "Identification et caractérisation d'une population de cellules lymphoïdes innées de type 2 (ILC2) associée à la sévérité de la rhinite allergique et de l'asthme." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS475.

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Identification et caractérisation d'une population d'ILC2 associée à la sévérité de la rhinite allergique et de l'asthmeTrois catégories de cellules lymphoïdes innées (innate lymphoid cells, ILC) ont été décrites récemment sur la base de leurs phénotypes et leurs caractéristiques fonctionnelles : les ILC1, ILC2 et ILC3. Les ILC2 semblent avoir un rôle pro-inflammatoire important dans l’allergie en raison de leur capacité à produire de grandes quantités de cytokines TH2.Pour mieux comprendre le rôle de ces cellules dans l’allergie respiratoire, nous avons comparé les ILC sanguines de patients atteints d’une rhinite allergique associée ou non à un asthme, à celles de sujets non allergiques. Cette étude révèle de multiples différences fonctionnelles entre les ILC circulantes de sujets sains et allergiques. Notamment, la fréquence d’ILC2 exprimant le récepteur aux chimiokines CCR10 est augmentée dans le sang de patients asthmatiques sévères.CCR10 pouvant permettre le recrutement des ILC vers les organes cibles, le rôle des ILC2 CCR10+ dans la physiopathologie de l’asthme a été étudié. Leur présence dans les poumons humains a été observée. Des analyses fonctionnelles et phénotypiques ont révélé que cette sous-population cellulaire était peu activée mais présentait une plasticité leur conférant des caractéristiques proches des ILC1. La déplétion de ces cellules dans un modèle murin d’asthme allergique aggrave l’hyperréactivité bronchique.Les travaux de cette thèse documentent le rôle des ILC dans l’asthme. En particulier, la fréquence sanguine d’ILC2 CCR10+ augmente avec la sévérité de la maladie. Les résultats obtenus dans les modèles animaux suggèrent que ces cellules auraient un rôle bénéfique dans le contrôle de l’asthme. La voie du CCR10 pourrait représenter une nouvelle cible pour le développement de traitements innovants contre l’asthme ou une source prometteuse de biomarqueurs
Identification and characterization of an ILC2 subset linked to allergic rhinitis and asthma severityInnate lymphoid cells (ILCs) have been classified into ILC1, ILC2 and ILC3 subsets based on their respective phenotypes and functions. Considering the strong ability of ILC2s to produce TH2 cytokines, these cells likely play a significant role in allergic diseases.To better understand the role of these cells in respiratory allergies, we compared blood ILCs from allergic patients with or without asthma to non-allergic individuals. Together our results show multiple functional differences between ILC from allergic and healthy subjects. In particular, ILC2s expressing the chemokine receptor CCR10 are specifically enriched in the blood of patients with severe allergic asthma.Considering that CCR10 could allow the recruitment of ILCs to target organs, the role of CCR10+ ILC2s in asthma physiopathology has been studied. This ILC2 subtype is present in human lungs. Functional and phenotypic analyses revealed that these cells are less activated than other ILC2s and show ILC1-like properties. CCR10+ ILC2s depletion in a mouse model of allergic asthma exacerbate airway hyperreactivity.Together, this work documents the role of ILCs in asthma. Specifically, circulating CCR10+ ILC2 frequency increases with asthma severity. The results obtained in mouse models suggest that these cells could have a beneficial role in asthma control. CCR10 pathway could represent a new target to elaborate breakthrough treatments against asthma or a source of promising biomarkers

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Gueguen, Claire. "Caractérisation des cellules dendritiques de type 2 : Application à la recherche de biomarqueurs de l’immunothérapie spécifique allergénique." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA114806.

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L’allergie ou l’hypersensibilité de type I est une réponse inappropriée du système immunitaire à une substance étrangère à l’organisme, nommée « allergène ». L’immunothérapie allergénique (ITA) est actuellement le seul traitement sur le marché qui permet de traiter l’étiologie de la maladie allergique par opposition aux traitements symptomatiques qui diminuent temporairement les manifestations allergiques. Son action consiste à réduire la sensibilité de l’organisme vis-à-vis de l’allergène en modulant progressivement la réponse immunitaire dirigée contre ce dernier. L’objectif de cette thèse était de définir des biomarqueurs d’efficacité clinique utilisables dans le cadre des traitements de l’ITA. La stratégie de recherche est basée sur une hypothèse qui consiste à suggérer que les cellules dendritiques (DCs) sont impliquées dans le succès de l’immunothérapie. En particulier, nous supposons que le traitement induit une baisse des DCs de type 2 (DC2), qui induisent des lymphocytes T auxiliaires de type 2 (TH2), et une augmentation des DCs régulatrices (DCreg), qui induisent des lymphocytes T régulateurs. La première partie de cette thèse a consisté à mettre au point des conditions de culture induisant des DC2. Pour cela, un criblage de molécules biologiques et pharmacologiques a été entrepris sur les DCs dérivées des monocytes afin d’induire in vitro des DC2 et a conduit à la mise au point d’un mélange de plusieurs molécules, dont certaines sont impliquées dans les mécanismes de l’allergie. Le phénotype des DC2 obtenu a été étudié ainsi que la polarisation des lymphocytes T induite après co-cultures en comparaison avec des DCs de type 1 (DC1) et des DCreg.La deuxième partie de cette thèse a consisté à analyser, à l’échelle moléculaire, les différents types de DCs induites (DC1, DC2 et DCreg). Pour cela, deux techniques ont été utilisées, une analyse transcriptomique par puces à ADN et une analyse protéomique par spectrométrie de masse sans marquage, pour comparer le transcriptome et le protéome des DCs induites. Le différentiel d’expression des marqueurs les plus pertinents a été validé au niveau transcriptionnel et protéique.Dans la troisième partie de cette thèse, le suivi des marqueurs dans des cellules du sang de patients allergiques traités ou non par ITA lors d’une étude clinique randomisée, contrôlée, en double aveugle, a permis de définir six nouveaux candidats biomarqueurs d’efficacité de l’immunothérapie, dont trois spécifiques des DC2 et trois autres spécifiques des DCreg. Ces marqueurs pourront être suivis lors des traitements d’ITA pour distinguer les patients répondeurs des non-répondeurs
Allergy or type I hypersensitivity is an inappropriate response of the immune system to a foreign substance in the body, called "allergen". Allergen immunotherapy (AIT) is currently the only treatment on the market that can handle the etiology of allergic disease versus symptomatic treatments that temporarily reduce allergic manifestations. Its action is to reduce the sensitivity of the body against allergens.The aim of this thesis was to define biomarkers of clinical efficacy of AIT. The research strategy is based on the following hypothesis: dendritic cells (DCs) are involved in the success of immunotherapy. In particular, we assume that the treatment induces a decrease in DCs type 2 (DC2), which induce type 2 helper T cells, and an increase of regulatory DCs (DCreg), which induce regulatory T cells.First, we defined optimal culture conditions inducing the polarization of in vitro immature monocyte-derived DCs (MoDCs) toward a DC2 pattern. After screening several biological and pharmaceutical agents, we selected a cocktail of six molecules with some of them are pro-allergenic molecules. The phenotype of those DC2 cells and the CD4+ T cell polarization induced after coculture were characterized extensively in comparison with type 1 DC (DC1) and DCreg.In a second part, we compared the transcriptomes and the proteomes of MoDCs polarized into DC1, DC2 and DCreg by using cDNA microarrays together with label-free mass spectrometry. The differential expression of the most relevant markers was confirmed at the transcriptional and protein level. In the third part, markers were also followed in the peripheral blood from allergic patients enrolled in a randomized, double-blind, placebo-controlled AIT study. The expression of three DC2 markers was down-regulated and of three DCreg markers was up-regulated in patients who responded to the treatment and correlated with clinical efficacy. These markers could be used as follow-up read-outs of AIT efficacy in order of to discriminate responders from nonresponders

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Lee-Fowler, Tekla. "Determination of allergen sensitization and comparison of subcutaneous and mucosal (intranasal) allergen-specific immunotherapy in an experimental model of feline asthma." Diss., Columbia, Mo. : University of Missouri-Columbia, 2009. http://hdl.handle.net/10355/6723.

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Thesis (M.S.)--University of Missouri-Columbia, 2009.
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "May 2009" Includes bibliographical references.

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Nony, Emmanuel. "Production et caractérisation de l'allergène recombinant Bet v 1 utilisé à des fins d'immunothérapie allergénique." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA114801.

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L'allergie respiratoire au pollen de bouleau affecte un nombre important de personnes dans le monde. Il est estimé que 100 millions d'individus sont sensibilisés à l'allergène majeur du pollen de bouleau nommé Bet v 1. L’immunothérapie allergénique, basée sur l'administration répétée de l'allergène incriminé, permet la rééducation du système immunitaire du patient d’un profil TH2 vers un profil TH1/Treg et à terme la diminution des symptômes allergiques. Ces travaux de thèse avaient donc pour finalité de produire et de caractériser l'allergène recombinant Bet v 1, à des fins d’immunothérapie allergénique. Dans ce cadre, différentes méthodes analytiques ont été développées et appliquées afin d'optimiser le procédé de production via l'élimination de différentes impuretés liées au produit ou au procédé de production et de documenter la structure de l’allergène. En particulier, l'utilisation de la spectrométrie de masse a permis la détermination de la masse exacte de l'allergène ainsi que la vérification complète de sa séquence en acides aminés. Les travaux en spectrométrie de masse ont également contribué aux détections et identifications de diverses impuretés et produits de dégradations et ont ainsi conduit à plusieurs optimisations du procédé industriel de production de l'allergène recombinant. Les activités immunologiques de certains produits de dégradations ont également été investiguées. La structure tertiaire (spatiale) de l'allergène a été déterminée par diffraction aux rayons X. Enfin, ces travaux ont permis de documenter la qualité de l'allergène recombinant rBet v 1 afin i) de l'établir comme substance de référence pour la Pharmacopée Européenne et ii) de procéder à une étude clinique d’immunothérapie allergénique de phase II auprès de 483 patients allergiques au pollen de bouleau
Respiratory allergy to birch pollen affects a large number of people in the world. It is estimated that 100 million people are sensitized to the major allergen from birch pollen, namely Bet v 1. Allergen immunotherapy, based on the repeated administration of the allergen of interest, allows the modification of the patient's immune response from a TH2 to a TH1/Treg pattern and thus the reduction of allergic symptoms. This study was therefore aimed to produce and characterize the recombinant Bet v 1 (rBet v 1) allergen, for immunotherapy purpose.In this context, various analytical methods have been developed and applied in order to optimize the production of rBet v 1 via the reduction of process or product-related impurities as well as to document the quality of the purified allergen. In particular, the use of mass spectrometry has allowed the determination of the exact mass of the intact allergen and the complete verification of its amino acid sequence. Mass spectrometry data have also contributed to the detection and identification of impurities and degradation products and have therefore led to several optimizations of the industrial process for the production of the recombinant allergen. Immunological activities of certain degradation products were also investigated and the allergen tertiary structure was determined by X-ray diffraction. Finally, this study was decisive in order i) to establish rBet v 1 as a chemical reference substance for the European Pharmacopoeia as well as ii) to perform a phase II clinical study conducted in 483 patients with birch pollen-induced rhinoconjunctivitis

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Sayers, Rebekah. "Proteomic profiling of processing-induced modifications to food proteins." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/proteomic-profiling-of-processinginduced-modifications-to-food-proteins(f6560c3b-4f80-49b9-94c2-6cd9b41288fa).html.

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Peanut allergy typically results from sensitisation to one or more integral seed storage proteins; Ara h 1, 3 or 2/6. Reactions can be triggered by as little as 3 mg protein in 10% of allergic individuals and are often severe, inducing anaphylaxis which can be fatal. Accidental exposure through unintended presence can therefore be hazardous and foods must be labelled appropriately. Thermal processing is one of the main factors affecting protein properties in food systems, including the formation of Maillard reaction products. Research has suggested a link between the allergenicity of foods and cooking methods employed. A systematic study was undertaken to assess the thermal dependence of these hazard proteins, focusing on changes to solubility and chemical modifications which may alter IgE binding. Proteomic profiling was used to assess the allergenic content of peanut products and develop alternative methods for allergen analysis to support evidence-based application of precautionary allergen labelling. Runner variety peanuts were processed (boiled, fried, roasted) and their protein content determined. Proteins extracts were characterised by 1D- and 2D-polyacrylamide gel electrophoresis, including differential in-gel electrophoresis. Proteomic profiling was undertaken using label-free analysis to assess allergen composition and investigate the formation of Maillard reaction products on the most clinically relevant proteins. Peanut allergen peptide targets were then identified and used to develop label-based quantitation methods and applied to (i) investigate effects of processing on peptide targets and (ii) determine peanut in chocolate products in comparison with a commercial ELISA kit. Orthogonal studies were performed using serum samples from peanut allergic patients obtained from the Manchester Respiratory, Allergy and Thoracic Surgery (ManARTS) Biobank. Patient IgE reactivity to peanut and processed peanut products was assessed by immunoblotting, inhibition ELISA and mediator release assays. Protein solubility was reduced by thermal processing and processed protein required harsh denaturing conditions for extraction. Qualitative analysis highlighted decreased solubility of key allergens, modifications and aggregation after heating. Proteomic profiling identified and quantified different isoforms of the major peanut allergens. The protein content of processed peanuts was reduced by boiling, specifically the 2S albumins, which transferred into the cooking water. The performance of peptides selected for targeted MRM experiments was influenced by thermal processing and the presence of cocoa phenolics. Ara h 2 peptides flanked by arginine were thermostable and may prove more reliable for quantification. Application of microfluidic separation enhanced the efficiency of target ionisation in complex matrices acquiring important sensitivity gains. Maillard modifications to clinically relevant proteins Ara h 2/6 were found within IgE binding domains in raw and processed peanuts. IgE reactivity studies confirmed reduced IgE binding capacity of extensively boiled peanut and hydrolysed protein, but this did not correlate to a reduction in mediator release in poly-sensitised patients. While effective extraction limits the efficacy of analyses, buffers used in MS analyses are more robust in analysing processed protein. Proteomic profiling provides a means of characterising and profiling of allergenic proteins including food ingredients used in clinical applications. Peptides selected for targeted analyses should be validated to assess their suitability in model foods. Cooking waters collected from extensively boiled peanuts may provide an alternative and safer immunotherapy agent for patients predominantly sensitised to Ara h 2/6.

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Scadding, Guy. "Nasal allergen provocation : validation of clinical and immunologic markers and response to grass pollen immunotherapy." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/33795.

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Background: Allergen-specific immunotherapy is an effective treatment for seasonal allergic rhinitis. Clinical trials may be confounded by variable allergen exposure. Nasal allergen provocation might provide a useful surrogate to assess the efficacy of immunotherapy and identify biomarkers of response. Objective: Nasal allergen provocation was used to assess the efficacy of allergen immunotherapy and identify local and systemic immune biomarkers. Methods: Dose and time course responses to grass-pollen nasal provocations were studied in 20 allergic individuals. Different matrices were compared for absorption and isolation of nasal mucosal fluid for immunoassay of inflammatory mediators. Optimised techniques were then applied to cat-allergen nasal provocation in 18 allergic individuals, along with assessment of in vitro basophil allergen-induced activation. Finally, in a cross-sectional study, responses to grass-pollen provocation were compared in 14 untreated grass-pollen allergics, 18 immunotherapy-treated patients, and 14 non-atopic controls. Results: Nasal responses to allergen were dose-dependent. Symptoms peaked at 5 minutes post challenge; overall, there was no distinct late-phase clinical response. Nasal fluid tryptase peaked at 5 minutes; IL-4, -5, -9, -13 and eotaxin peaked at 8 hours. Basophil allergen-induced activation in vitro was enhanced at 6 hours compared to pre-challenge. Grass-pollen immunotherapy-treated patients had lower symptom scores (45% lower, p=0.04) and higher peak nasal inspiratory flow, PNIF (54% higher, p=0.02) after challenge than untreated-allergics. They had reduced early (27% lower, p=0.0007) and late (51% lower, p < 0.0001) skin responses, and lower retrospective seasonal symptom scores (60% lower, p < 0.0001). Nasal challenge response correlated with seasonal symptoms (symptoms: r=0.52, p < 0.003; PNIF: r=-0.57, p < 0.001). Immunotherapy-treated patients had reduced nasal fluid IL-4, IL-9 and eotaxin (p < 0.05), and trends for reduced IL-13 and tryptase levels (p=0.07). Conclusions: Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.

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Junebjörk, Lydia, and Johanna Marstorp. "Patienters upplevelser av allergenspecifik immunterapi." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-294566.

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Introduktion: I Sverige har det uppmätts att 27% av befolkningen har en luftvägsallergi. Dessa behandlas främst med symtomlindrande läkemedel men när detta inte räcker till kan allergenspecifik immunterapi (ASIT) övervägas. Denna behandling kan ges antingen sublingualt eller med subkutana injektioner. Den första studien om ASIT publicerades 1911 och sedan dess har många studier gjorts angående dess effekter. Syfte: Syftet med studien var att undersöka patienters upplevelser av subkutan immunterapi (SCIT). De områden som belystes var upplevelsen av information och kommunikation, psykisk och fysisk påverkan av biverkningar samt hur behandlingen inverkar på vardagen. Metod: En kvalitativ studiedesign användes och data samlades in med hjälp av semistrukturerade intervjuer. Ett bekvämlighetsurval gjordes på en allergimottagning i Mellansverige och tio personer intervjuades. Resultat: Behandlingen påverkade somliga delar av vardagen i viss mån, till exempel att det är tidskrävande och att den fysiska aktiviteten blir begränsad under behandlingsdagen. En del biverkningar förekom, främst allmänna och lokala. Dessa hade viss påverkan på vardagen relaterat till exempelvis trötthet och koncentrationssvårigheter. Kontakten med mottagningen upplevdes positivt och informationen som erhölls inför behandlingsstart upplevdes som tillräcklig. Dock framkom att informationen kring allvarligare biverkningar inte nått fram till alla. Slutsats: Både de upplevda biverkningarna och behandlingen som helhet hade en viss påverkan på patienternas vardag. Kommunikationen och informationen från vården upplevdes överlag positivt. Vidare forskning inom området behövs för att kunna avgöra om dessa resultat är överförbara till en bredare population.
Introduction: It has been measured that 27% of the population in Sweden has a respiratory allergy. Primarily this is treated symptomatically with medication but in cases where this do not work, allergen specific immunotherapy (ASIT) can be considered. ASIT can be administered either sublingually or subcutaneously. The first study acknowledging ASIT was published in 1911 and since then many studies have been performed regarding its effects. Aim: The aim of this study was to examine patients experiences of subcutaneous immunotherapy (SCIT). This included how patients experienced information and communication, how side-effects affected patients physically and psychologically and how the treatment affected the patients’ everyday life. Methods: A qualitative study design was used and data was collected with semi-structured interviews. A convenience sample was made at an allergy reception in central Sweden and ten people were interviewed. Results: Parts of the patients’ everyday life were affected to some extent, for example because the treatment is time consuming and that the physical activity has to be limited during the same day as the injection is given. Some side-effects occurred, primarily general and local ones. These affected the everyday life in the sense that the patients felt tired and experienced difficulty concentrating. The contact with the reception was described in a positive manner and the information received before starting treatment was described to be enough. Although the information regarding serious side-effects had not been reached by everyone. Conclusion: Both the experienced side-effects and the treatment in its whole had a certain impact on the patients’ everyday life. The patients described the communication and the information in a positive way. More studies need to be performed in this field to be able to determine whether these results are transferable to a broader population.

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Pinto, Marta. "Epicutaneous immunotherapy as a novel route of allergen administration in dogs with atopic dermatitis : a proof-of-concept study." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2021. http://hdl.handle.net/10400.5/22140.

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Dissertação de Mestrado Integrado em Medicina Veterinária
ABSTRACT - Allergen immunotherapy is a well-established treatment for canine atopic dermatitis (CAD), but new non-invasive, safe, effective and at-home easy-to-use vaccine-delivery routes that promote compliance are needed. Epicutaneous immunotherapy (EPIT) is a new promising alternative route that takes advantage of the skin’s unique immunological features and high accessibility. Our goal was to assess the feasibility, efficacy, and safety of EPIT in CAD. Sixteen dogs (9 French bulldog (FB) and 7 labrador retriever (LR) dogs) with spontaneous non seasonal CAD and positive allergen-specific IgE (sIgE) serology for domestic mites (HDM) were enrolled for a weekly, 12-hour allergen-containing patch application, over 12 weeks. A costume-made 3D-printed device was developed to incorporate the allergen-based formulation, which included a tailor-made vehicle to enhance allergen penetration into the skin. The primary efficacy outcomes were the owner-assessed pruritus manifestations (PVAS10), veterinarian-assessed skin lesions (2D-IGA), and the owner’s perceived treatment efficacy (OGATE and OGES). Secondary efficacy outcomes were the quality-of-life (QoL), sIgE and IL 10 concentrations. The EPIT safety evaluation considered both local and systemic adverse reactions. Treatment efficacy was defined by the primary outcome measures’ success, according to the ICADA’s COSCAD’18 recommendations. EPIT was deemed safe if no severe local and systemic side-effects occurred. The owner’s compliance with the proposed protocol and required study appointments were monitored and their overall satisfaction was estimated. One LR dog dropped out. All dogs improved their pruritus scores, and 13/15 dogs (86.67%) were successful in the terms considered for this study [FB=8/9 (88.89%); LR=5/6 (83.33%)]. Moreover, 8/12 dogs [66.67%; FB=5/8 (62.5%); LR=3/4 (75%)] reached the level considered successful in the skin lesions’ sore. The response to EPIT was rated as good-to-excellent by 13/15 owners (86.67%) in the OGATE survey and by 11/15 owners (73.33%) in the OGES survey. An improvement in the QoL scores was reported by 13/15 owners (86.67%), with a percentage mean improvement of 54.58%. sIgE values overall decreased in 10/15 dogs (66.67%) and 2/15 dogs (13.33%) desensitised to all HDM to which they were previously allergic. Non-conclusive IL-10 results were obtained. No systemic or local severe adverse events were recorded. EPIT was well received by the owners of the 15 dogs, who fully complied with the proposed protocol. This pilot study emphasizes the EPIT’s great potential as an effective and safe CAD treatment, supporting further investigation on this novel therapy.
RESUMO - Imunoterapia epicutânea como uma nova via de administração de alergénios em cães com dermatite atópica : uma prova de conceito - A imunoterapia com alergénios é um tratamento bem estabelecido para a dermatite atópica canina (CAD), mas são necessárias novas vias não invasivas, seguras, eficazes e de fácil administração em casa que promovam a adesão à terapia. A imunoterapia epicutânea (EPIT) é uma via promissora que beneficia da grande acessibilidade e das características imunológicas únicas da pele. O objetivo deste estudo foi avaliar a praticabilidade, eficácia e segurança da EPIT na CAD. Foram recrutados dezasseis cães (9 cães bouledogue francês (FB) e 7 labrador retriever (LR)) com CAD espontânea não sazonal e com serologia de IgE alergénio-específica (sIgE) positiva para ácaros domésticos (HDM) para a aplicação semanal de um penso de 12 horas, durante 12 semanas. Para o efeito foi impresso um dispositivo em 3D para incorporar a formulação alergénica, a qual incluía um veículo desenvolvido para aumentar a penetração dos alergénios na pele. A avaliação da eficácia utilizou parâmetros primários – a avaliação do prurido pelo titular do cão (PVAS10), das lesões cutâneas pelo veterinário (2D-IGA) e a perceção dos titulares sobre a eficácia da terapêutica (OGATE e OGES) – e parâmetros secundários – grau de qualidade de vida e concentrações de sIgE e IL-10. Para a avaliação da segurança foram consideradas reações sistémicas e locais. A eficácia da EPIT foi definida pelo sucesso dos parâmetros primários, de acordo com as recomendações COSCAD’18 do ICADA. A EPIT foi considerada segura se não ocorressem reações sistémicas ou locais graves. Foram ainda registados o cumprimento do protocolo, a comparência dos titulares às consultas do estudo e a sua satisfação global com o tratamento. Um titular de LR desistiu do estudo. Todos os cães melhoraram o grau de prurido, dos quais 13 (86.67%) alcançaram o nível considerado de sucesso [FB=8/9 (88.89%); LR=5/6 (83.33%)]. Além disso, 8 dos 12 cães [66.67%; FB=5/8 (62.5%); LR=3/4 (75%)] alcançaram o nível considerado de sucesso no parâmetro de lesões cutâneas. A resposta à EPIT foi classificada como boa-a-excelente por 13 titulares (86.67%) no OGATE e por 11 titulares (73.33%) no OGES. Verificou-se ainda uma melhoria da qualidade de vida em 13 cães (86,67%), com uma melhoria percentual média de 54.58%. Os valores de sIgE diminuíram globalmente em 10 cães (66.67%) e 2 deles (13.33%) dessensibilizaram a todos os HDM aos quais eram alérgicos. Os resultados da IL-10 foram inconclusivos. Não se verificaram quaisquer reações sistémicas nem locais graves. A EPIT foi bem recebida pelos titulares dos 15 cães, os quais cumpriram criteriosamente o protocolo. Este estudo piloto destaca o potencial da EPIT como um tratamento eficaz e seguro para a CAD e encoraja a investigação futura nesta nova terapia.
Supported by LETIPharma Animal Health S.L.U. (Barcelona, Spain)
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Caillot, Noémie. "Identification, caractérisation et validation de biomarqueurs liés à l’immunothérapie allergénique." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA114805/document.

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Cette thèse a pour objectif d’identifier et caractériser des biomarqueurs liés aux traitements d’immunothérapie allergénique (ITA). En particulier, le travail s’est porté sur les biomarqueurs prédictifs de l’efficacité du traitement : leur estimation avant la prise médicamenteuse permettrait d’évaluer les bénéfices cliniques à l’issue de l’ITA. À partir d’échantillons de sérum collectés avant ITA et provenant de patients inclus dans une étude clinique contrôlée, randomisée et dirigée contre les pollens de graminées, une méthode d’analyse protéomique différentielle (la 2D-DIGE) a permis d’identifier une protéine comme candidat biomarqueur prédictif de l’efficacité de l’ITA. Dans un premier temps, les variants moléculaires de la protéine identifiée ont été caractérisés. L’analyse en spectrométrie de masse de la protéine a permis d’identifier les modifications post-Traductionnelles associées aux isoformes plus abondants dans le sérum des patients pour lesquels une réponse positive à l’ITA est observée. Une approche protéomique de quantification relative a été mise en œuvre par LC-MS/MS sans marquage, et a permis d’identifier des peptides de la protéine d’intérêt, portant des modifications post-Traductionnelles spécifiques, associés à un bénéfice clinique accru en fin d’ITA. Dans un deuxième temps, l’implication de la fétuine-A dans la physiopathologie de l’allergie a été étudiée. Des modèles cellulaires humains ont mis en évidence le caractère essentiel des acides sialiques portés par la protéine pour l’activation de la voie TLR4, dans les mécanismes de l’immunité innée initiant la réaction allergique. In vivo, les modèles murins d’asthme allergique développés ont en revanche montré la fonction anti-Inflammatoire de la protéine. La fétuine-A a donc un rôle ambivalent, mais est indubitablement liée à la régulation de l’inflammation allergique. La validation des candidats biomarqueurs peptidiques de la protéine dans d’autres cohortes cliniques représente une future étape clé, qui permettrait d’envisager l’usage de ces marqueurs en clinique, pour améliorer la sélection des patients les plus susceptibles de répondre à l’ITA
This thesis aimed at identifying and characterizing predictive biomarkers associated with allergen-Specific immunotherapy (AIT) efficacy. In particular, we were focused on biomarkers predictive of AIT efficacy: quantifying such markers before treatment would allow estimating the final clinical benefit. For this purpose, serum samples were collected before AIT from patients included in a double-Blind, placebo controlled clinical study against grass pollen allergy. Their analysis by means of differential proteomics (2D-DIGE) pointed out a protein, named fetuin-A, as a candidate biomarker predictive of AIT efficacy. First, the protein fetuin-A isoforms were extensively characterized by mass spectrometry, and specific post-Translational modifications (PTMs) were associated to the isoforms more abundant in sera from patients positively responding to AIT. A second proteomic approach allowed identifying fetuin-A peptides, differentially expressed among groups of patients. Some peptides from the candidate protein, bearing specific post-Translational modifications (PTMs), are associated with an increased clinical benefit at the end of the treatment. In a second part, we studied the involvement of the fetuin-A during the course of allergic inflammation. Human cellular assays highlighted that sialic acids on the protein PTMs are essential to activate the TLR4 pathway, and inducing innate immune mechanisms linked to allergy. In vivo, murine models of allergic asthma showed an opposite anti-Inflammatory function of the protein. Thus, the protein fetuin-A is still ambivalent, but is undoubtedly linked to the regulation of allergic inflammation. Validation of peptides candidate biomarkers in larger clinical cohorts is of utmost interest, since using such biomarkers in clinics would improve patients’ selection and therefore clinical benefit from the treatment

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Wang, Shu-Hung [Verfasser], Carsten [Akademischer Betreuer] Schmidt-Weber, Dietmar [Gutachter] Zehn, and Caspar [Gutachter] Ohnmacht. "Transitional T Cell Phenotypes in Allergen-specific Immunotherapy / Shu-Hung Wang ; Gutachter: Dietmar Zehn, Caspar Ohnmacht ; Betreuer: Carsten Schmidt-Weber." München : Universitätsbibliothek der TU München, 2021. http://d-nb.info/1230985395/34.

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Plancha, André Alexandre Morais. "Clínica e cirurgia em animais de companhia." Master's thesis, Universidade de Évora, 2019. http://hdl.handle.net/10174/26362.

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Este relatório foi realizado após o estágio curricular realizado no Hospital Mediterranis Veterinaris (HMV) de janeiro a maio de 2018. Na primeira parte refere-se a casuística acompanhada ao longo do mesmo e numa segunda a monografia sobre dermatite atópica canina (DAc). A terceira parte inclui um caso clínico sobre o tema antes citado. A DAc é uma doença inflamatória e pruriginosa da pele, com predisposição genética e sinais clínicos característicos, frequentemente associados a anticorpos IgE produzidos em resposta a alergénios ambientais. O diagnóstico é baseado numa história típica de DAc com sinais clínicos campatíveis (lesões e respetiva destribuição) descartando outras dermatoses pruríticas. A importância dos testes alergológicos recai na escolha dos alergénios a incluir na imunoterapia e nas medidas de prevenção alergénica, uma vez que a doença é incurável; ABSTRACT: This report was carried out after the curricular internship at the Hospital Mediterranis Veterinaris (HMV) from January to May of 2018. The first segment refers to all the clinical cases followed along that time, and the second one to a monography on canine atopic dermatitis (CAD). The third part contains a clinical example on this subject. CAD is an inflammatory disease that goes along with an itchy skin condition. It has a genetic predisposition and characteristic clinical signs, most commonly associated with IgE antibodies in response to environmental allergens. The diagnosis is based on typical CAD clinical history, with compatible signs (lesions and their distribution) discarding other pruritic dermatosis. The allergic exams used on those cases are extremely important for the election of the allergens to include on the immunotherapy and for the preventive measures, since the disease is incurable.

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Silva, Catarina Tusto Cordeiro Borges da. "Imunoterapia específica para alergénios como terapêutica da dermatite atópica canina : situação actual de conhecimentos dos médicos veterinários e dos proprietários." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2011. http://hdl.handle.net/10400.5/3005.

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Dissertação de Mestrado Integrado em Medicina Veterinária
A dermatite atópica canina (cDA) é a doença atópica mais frequentemente diagnosticada no cão e pensa-se que o número de casos seja cada vez maior. A imunoterapia específica para alergénios (ITAE) consiste na administração de quantidades, gradualmente crescentes, de um alergénio, de forma a atenuar os sinais clínicos de cDA. A fim de se alcançar uma maior eficácia, esta terapêutica deve ser ajustada para cada caso. Assim, a escolha dos alergénios a incluir e do protocolo a seguir deve ser criteriosamente efectuada, tendo em conta a história clínica, o ambiente e a reacção individual de cada paciente. Este estudo teve como objectivo caracterizar a utilização da ITAE por parte dos Médicos Veterinários (MV) e tentar esclarecer se os conceitos acima descritos são aplicados na prática clínica corrente. Pretendeu-se também avaliar os proprietários dos pacientes alérgicos em relação aos seus conhecimentos sobre a ITAE e à vontade que demonstraram em aderir a esta terapêutica. No caso dos proprietários de animais que já realizaram ITAE durante um período mínimo de 6 meses, analisou-se o seu grau de satisfação com o tratamento. Para tal, foram realizados inquéritos a MVs, a proprietários de animais com cDA e a proprietários de animais que já realizaram ITAE. Concluiu-se que o conceito de ajustamento da ITAE a cada paciente não se encontra ainda bem esclarecido na classe Médico Veterinária. De facto, a maioria dos MVs não opta por ajustar o protocolo de administração e elegem os alergénios a incluir no tratamento exclusivamente com base nos resultados positivos das provas alergológicas. Os proprietários de pacientes com cDA têm uma opinião positiva sobre a ITAE e estão dispostos a aderir a esta. O nível de informação e de satisfação dos proprietários cujos animais já foram submetidos a este tratamento é elevado. Verificaram-se, assim, algumas lacunas na utilização da ITAE, pelo que se sugere que haja uma maior educação dos MVs sobre os aspectos práticos desta terapêutica, uma vez que estes se reflectem directamente na sua eficácia, sendo no entanto pouco valorizados pela generalidade dos clínicos. É também importante apostar na informação dos proprietários, com o intuito de aumentar a cooperação por parte destes e de obter melhores resultados clínicos.
ABSTRACT - Allergen specific immunotherapy as a treatment of canine atopic dermatitis – present situation of Veterinarian´s and owner´s knowledge on the subject - Canine atopic dermatitis is the most frequently diagnosed atopic disease in dogs and it seems to be increasing in the canine population. Allergen specific immunotherapy is based on the administration of gradually increasing doses of allergens, with the purpose of alleviating the clinical signs of canine atopic dermatitis. In order to achieve a greater effectiveness, this treatment should be tailored individually to each patient. Therefore, the allergens included and the protocol followed should be chosen carefully, taking into account the medical history, the environment and the individual reaction of each animal. The objective of this study was to analyze the use of immunotherapy by Veterinary clinicians and to verify if the above criteria are applied in current clinical practice. We also evaluated how much owners of allergic dogs know about this treatment and how willing they are to adhere to it. In those owners whose dogs had been submitted to immunotherapy for a period of at least six months, we wanted to know if they were satisfied with this treatment. Therefore, surveys were carried out to Veterinarians and owners of dogs which suffer from atopic dermatitis and which have undergone specific immunotherapy. We conclude that immunotherapy is not being individualized to each patient by most clinicians. In most cases the choice of the allergens is based on the positive titles of the serum-based tests, regardless of seasonality of clinical signs. The owners of dogs with atopic dermatitis have a good opinion of immunotherapy and are willing to adhere to it. Also the owners of dogs that have done this treatment demonstrated high levels of information and satisfaction. It is suggested that Veterinarians should pursue higher levels of education regarding the practical aspects of immunotherapy, which reflect on its effectiveness and are nonetheless not being taken into account in clinical practice. . It is also suggested to invest in the information of the owners as we also believe that client education is paramount to increase their cooperation and achieve better clinical results.

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Groeme, Rachel. "Production et caractérisation structurale et fonctionnelle d’un nouvel allergène majeur du pollen d’Ambroisie : la protéase à cystéine Amb a 11." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLA006.

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Le projet de thèse à pour but de produire et caractériser un nouvel allergène de pollen d'ambroisie. Le projet est décliné en cinq axes: production d'une forme recombinante mature et en conformation native, caractérisation structurale, étude de la fonction enzymatique, étude de l'allergenicité et l'immunogénicité et évaluation du potentiel thérapeutique
The goal of the thesis project is to product and caracterize a novel ragweed pollen allergen.The project have five axes: production of recombinant mature and native form,structurale caracterization, study of enzymatique function, study of allergenicity and immunogenicity and evaluation of therapeutic potential

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Ferrell, Melissa Leann. "Sublingual Immunotherapy." Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/565918.

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One of the most common reasons people seek primary care and emergency care is to reduce the symptoms of allergies, such as hay fever. To meet this high demand, several recent FDA-approved methods for treating seasonal and perennial allergies have been developed, including sublingual immunotherapy tablets. Furthermore, no longer must a patient endure allergy shots; this can now be delivered sublingually. Although this method has been shown to have high safety and efficacy, very few clinicians actually utilize this form of therapy. The purpose of this paper is describe the use of sublingual immunotherapy among Nurse Practitioners (NPs) and discuss barriers that may prevent its use. Nurse Practitioners working in primary care settings were surveyed regarding their use of sublingual immunotherapy. Although many nurse practitioners treat patients with allergic disease, not one participant reported using sublingual immunotherapy. This discussion outlines some of the reasons NPs are not currently utilizing this method of allergy treatment and the findings are compared with the extant literature. This paper culminates in an evidence-based algorithm to outline best practices for utilizing sublingual immunotherapy to reduce allergy symptoms.

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Vicente, Marisa Alexandra Nunes. "Resultados de imunoterapia alergénio-específica sublingual em canídeos atópicos, no concelho de Oeiras : estudo piloto." Master's thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2015. http://hdl.handle.net/10400.5/8998.

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Dissertação de Mestrado Integrado em Medicina Veterinária
A dermatite atópica canina (DAc) é uma doença de incidência elevada e crescente na população canina. A par da evicção alergénica, frequentemente inviável, a imunoterapia alergénio-específica (ITAE) é o único tratamento passível de modificar o curso natural da doença a longo prazo, mesmo após a sua suspensão. A via de administração tradicional de ITAE é a injeção subcutânea; no entanto, a via sublingual (SLIT) tem vindo a ganhar cada vez mais adeptos na comunidade médica devido à sua proclamada maior segurança, praticabilidade e conforto na aplicação. O principal objetivo deste estudo retrospetivo centrou-se na avaliação da eficácia de um protocolo inicial de 7 meses de SLIT em 22 canídeos atópicos. Numa primeira fase procedeu-se a análise epidemiológica dos painéis alérgicos de 72 canídeos diagnosticados clinicamente com DAc e submetidos a provas alergológicas serológicas. Destes, 16,7% resultaram num painel alérgico negativo a todos os aeroalergénios testados. Na amostra analisada não houve predomínio de género e a raça indeterminada e o Retriever do Labrador foram as mais prevalentes. O grupo de alergénios mais frequentemente envolvido no processo alérgico foi o dos ácaros, nomeadamente as espécies Dermatophagoides farinae, Acarus siro e Tyrophagus putrescentiae. Na segunda fase, analisou-se a resposta à terapêutica em 22 canídeos atópicos submetidos a um protocolo de 7 meses de SLIT, face a um grupo de controlo de 22 canídeos atópicos tratados exclusivamente com medicação antialérgica sintomática. Esta análise foi feita através de um questionário aplicado aos donos dos animais e através do grau de redução da necessidade de medicação antialérgica concomitante para controlo dos sinais clínicos de DAc. Obteve-se uma redução estatisticamente significativa dos níveis de prurido no grupo de estudo face ao grupo de controlo. Ainda, 31,8% dos animais conseguiram controlar os sinais clínicos de DAc com recurso apenas à SLIT ou, em alguns casos, combinada com champô hipoalergénico. De forma geral, 86,4% dos animais responderam positivamente ao tratamento com SLIT. No entanto, o período de 7 meses de tratamento foi insuficiente para prevenir recidivas após a suspensão, pelo que o mesmo deve ser alargado. Este estudo, apesar das suas limitações, contribui assim para o crescente volume de bibliografia que atesta a eficácia e segurança da SLIT, constituindo uma alternativa válida para o tratamento da DAc.
ABSTRACT - Results of a sublingual allergenic-specific immunotherapy protocol in atopic dogs in Oeiras, Portugal: a pilot study - Canine atopic dermatitis (cAD) is a disease with a high and increasing incidence in the canine population. Only allergenic avoidance, which is frequently not viable, and allergenspecific immunotherapy (ASIT) can affect the natural course of allergic diseases, even after treatment interruption. Subcutaneous injections are the traditional route of ASIT administration; however the medical community’s interest in sublingual administration (SLIT) is growing due to its high safety profile, practicability and more comfortable administration. The main purpose of this retrospective study was to evaluate the response to a 7-month SLIT protocol executed upon 22 atopic dogs. Initially (stage 1), we conducted an epidemiological analysis on the allergenic results of 72 dogs diagnosed with cAD, both clinically and through serological testing. From these, 16,7% had negative results to all allergens tested. In our sample, no sex predisposition was found, plus crossbreed dogs and Labrador retrievers were the most frequently affected out of the sample. Mites constituted the group of allergens mostly involved in the allergic pathway, specifically Dermatophagoides farinae, Acarus siro and Tyrophagus putrescentiae. In a second stage, we analyzed the treatment response of 22 atopic dogs that endured a 7- month SLIT protocol in comparison to a control group of 22 atopic dogs submitted only to an anti-allergic symptomatic drug treatment. This analysis was conducted using questionnaires presented to the dog’s owners and through the medical records, which allowed us to evaluate the need for anti-allergic medication in order to control the pruritus. We observed a significant statistical reduction in the level of pruritus in the study group, compared to the control group. Furthermore, in 31,8% of the dogs it was possible to control the clinical signs merely using SLIT or, in some cases, SLIT combined with a hypoallergenic shampoo. Overall, 86,4% of the dogs positively responded to SLIT. However, we concluded that the 7- month treatment period is not enough to prevent relapses after SLIT’s discontinuation and, therefore, the period of treatment should be longer. Despite the limitations, this study contributes to the growing body of evidence that supports the efficacy and safety of SLIT and considers it a viable alternative treatment in AD patients.

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Rußkamp, Dennis Matthias [Verfasser], Simon [Akademischer Betreuer] Blank, Sabine [Gutachter] Flicker, Simon [Gutachter] Blank, and Jörg [Gutachter] Durner. "Sustained Inhibition of the IL-4/IL-13 Receptor Complex during Allergen-Specific Immunotherapy / Dennis Matthias Rußkamp ; Gutachter: Sabine Flicker, Simon Blank, Jörg Durner ; Betreuer: Simon Blank." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1192911474/34.

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David, Susana Isabel Ribeiro. "Avaliação da eficácia de um protocolo rápido de imunoterapia alergénio-específica em cães atópicos." Master's thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2014. http://hdl.handle.net/10400.5/7194.

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Dissertação de Mestrado Integrado em Medicina Veterinária
A dermatite atópica canina (DAc), doença cutânea com grande expressão no Cão, tem um forte impacto na qualidade de vida dos pacientes. A imunoterapia alergénio-específica (ITAE), que tem uma eficácia entre os 60 e 80% e uma baixa incidência de efeitos secundários, é a única forma de tratamento da DAc capaz de induzir um estado de verdadeira remissão clínica. Os protocolos rápidos permitem abreviar a fase de indução e assim obter uma resposta clínica mais precoce. O estado de tolerância imunitária induzido pela ITAE é alcançado através de um desvio para uma resposta de tipo TH1, produção de outras classes de imunoglobulinas e estimulação de linfócitos T reguladores. Os mediadores inflamatórios produzidos são determinantes para o sucesso terapêutico. A eficácia de um protocolo de ITAE pode ser avaliada através do valor de CADESI-03, grau de prurido e pelos níveis séricos de mediadores inflamatórios. Destes, pode destacar-se a IL-10, citocina muito importante na homeostasia imunitária em indivíduos saudáveis e que desempenha um papel crucial na maioria dos mecanismos de acção da ITAE. Neste trabalho, 14 cães atópicos foram submetidos a um protocolo rápido de ITAE e reavaliados passadas 4 e 12 semanas. Diferenças estatisticamente significativas no grau de prurido (p≤0,05) foram registadas 4 semanas após o início do tratamento e às 12 semanas para o valor de CADESI-03 (p≤0,05). As concentrações séricas de IL-10 revelaram-se inconclusivas. A resposta à ITAE parece ser tão mais precoce quanto mais abreviada for a fase de indução do protocolo.
ABSTRACT - EVALUATING THE EFFECTIVNESS OF AN RUSH ALLERGEN-SPECIFIC IMMUNOTHERAPY PROTOCOL IN ATOPIC DOGS - Canine atopic dermatitis (cAD), is a very prevalent skin disease in dogs and has a strong impact on patient quality of life. Allergen-specific immunotherapy (ASIT) is efficacious in about 60 to 80% and presents a low incidence of side effects. Also, is the only treatment for cAD with ability to induce a state of true clinical remission. Rush protocols allow shorter induction phases and thereby earlier clinical responses. The state of immune tolerance induced by ASIT is achieved by a shift to a TH1 like response, production of other immunoglobulin classes and stimulation of regulatory T lymphocytes. The produced inflammatory mediators are crucial to therapeutic success. The effectiveness of an ASIT protocol can be assessed by the CADESI-03 score, pruritus level and serum levels of inflammatory mediators. In particular we can highlight IL-10, important cytokine in the immune homeostasis in healthy individuals, which plays a crucial role in the most ASIT mechanisms of action. In this study, 14 atopic dogs performed a rush ASIT protocol and were re-evaluated after 4 and 12 weeks. Statistically significant differences in pruritus level (p ≤ 0.05) were recorded 4 weeks after treatment initiation and after 12 weeks for the CADESI-03 score (p ≤ 0.05). Serum levels of IL-10 were inconclusive. Response to ASIT seems to be achieved earlier with the shorten induction phase of the rush protocol.

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Michaud, Bénédicte. "Etude de la réponse lymphocytaire T dans l’allergie de l’enfant, au diagnostic et au cours de la désensibilisation." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T025/document.

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Les maladies allergiques sont de plus en plus fréquentent. Elles atteignent souvent l’enfant jeune chez qui l’allergie respiratoire et l’allergie alimentaire sont les principales pathologies. L’unique traitement curatif est l’immunothérapie spécifique d’antigène (ITA), largement développée dans l’allergie respiratoire et encore à ses débuts dans l’allergie alimentaire. Pour adapter au mieux la prise en charge du patient, le diagnostic précis de l’allergie est indispensable et il n’existe actuellement pas d’examen biologique totalement fiable. Seul, la présence d’IgE spécifiques permet de diagnostiquer une sensibilisation à un allergène mais pas une allergie cliniquement symptomatique. Dans une première partie, nous avons étudié l’intérêt d’un test fonctionnel, l’ELISpot (Enzyme-linked immunosorbent spot), dans le diagnostic de l’allergie aux acariens chez l’enfant asthmatique. Le nombre de lymphocytes T circulants spécifiques d’acariens sécréteur d’interleukine (IL)-4 ou d’IL-13 était associé à la présence d’une allergie symptomatique, indépendamment des IgE spécifiques. Il était plus élevé dans le cas d’une rhinite allergique sévère et plus faible dans le cas d’une rhinite allergique légère. De plus, il variait au cours de l’année en fonction des saisons avec un pic en automne et un pic en début de printemps. Dans une deuxième partie, nous avons étudié l’intérêt de l’ELISpot dans le diagnostic de l’allergie au lait de vache chez l’enfant, confirmée par un test de provocation orale en double aveugle. Nous avons décrit que le nombre de lymphocytes T spécifiques de la caséine et sécréteurs d’IL-4 et d’IL-13 était associé à l’allergie au lait de vache avec une sensibilité de 100%. Par ailleurs, le nombre de lymphocytes T spécifiques de la caséine était également associé à la dose maximale de lait tolérée par l’enfant.Enfin, dans une troisième partie, nous avons étudié la réponse lymphocytaire T au cours d’une ITA sub-linguale (SLIT) d’une part et sous-cutanée (SCIT) d’autre part, chez des enfants asthmatiques allergiques aux acariens suivis pendant une année. Nous avons décrit une diminution des lymphocytes Th2 (sécréteurs d’IL-4 et IL-13) spécifiques d’acariens après 12 mois de SLIT associée à une augmentation des cellules sécrétrices d’IL-10 (Tr1) spécifiques d’acariens après 6 mois de SLIT. De plus, les lymphocytes T régulateurs (CD4+CD25hiCD127loFoxp3+) étaient augmentés après 12 mois de SCIT. Nous n’avons pas retrouvé de production accrue d’interféron γ (IFNγ) par les lymphocytes T spécifiques d’acariens au cours de la désensibilisation.Au total, ce travail nous a permis de décrire qu’un test fonctionnel, l’ELISpot, permet de réaliser un diagnostic fiable de l’allergie aux acariens et de l’allergie au lait de vache chez l’enfant. Par ailleurs, l’ITA induit une diminution des cellules Th2 et une augmentation des cellules Tr1 par voie sub-linguale ainsi qu’une augmentation des Treg Foxp3+ par voie sous-cutanée sans immunodéviation Th2/Th1, chez l’enfant allergique aux acariens
Allergic diseases are steadily increasing steadily and especially in children. Allergen specific immunotherapy (desensitization) is the only curative treatment for which accurate diagnosis of allergy is essential. Currently, the presence of specific IgE diagnoses a sensitization to an allergen but not a clinically symptomatic allergy. In a first part, we studied the value of a functional test, the ELISpot (Enzyme-linked immunosorbent spot) in the diagnosis of allergy to house dust mites (HDM). The number of circulating HDM-specific IL-4 and IL-13 secreting T cells was associated with the presence of symptoms, regardless of specific IgE and was higher in severe rhinitis than in mild rhinitis. In addition, it varied according to the season with a peak in autumn and a peak in early spring (wet periods with greater allergen exposure). In a second part, we studied the value of ELISpot for the diagnosis of cow's milk allergy in children, confirmed by double blind placebo control food challenge. We found that the number of casein-specific IL-4 and IL -13 secreting T-cells was associated with allergy to cow's milk. It was also inversely correlated to the cow’s milk tolerated cumulative dose. Receiver-operating characteristic (ROC) curve of combined IL-4 and IL-13 analysis was generated. AUC was 0,98 (95% CI 0.90-1.06). For a cut-off of 10 IL-4- and 12 IL-13 secreting T-cells, sensitivity and negative predictive value were 100%.Finally, in the third part, we monitored antigen specific T-cell response in HDM allergic children treated with sublingual ITA (SLIT) on the one hand and subcutaneous ITA (SCIT) on the other hand, during one year. We found a decrease in HDM specific Th2 cells after 12 months of SLIT associated with an increase in HDM specific IL-10 secreting T-cells after 6 months of SLIT. In addition, regulatory T cells (CD4 + CD25hiCD127loFoxp3+) were increased after 12 months of SCIT. In conclusion, this work has allowed us to describe a functional test, the ELISpot, as a reliable tool for the diagnosis of mite allergy and cow's milk allergy in children. In addition, in HDM allergic children, a decrease of Th2 cells and an increase of IL-10 secreting T-cells was found in children treated with SLIT to HDM as well as an increase in Foxp3+ Treg in children treated with SCIT

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Grönlund, Hans. "Diagnosis and treatment of IgE-mediated allergy : new approaches using recombinant allergens /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-373-6/.

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Mahay, Guillaume. "Etude de l'initiation de la tolérance de l'immunothérapie spécifique aux venins d'hyménoptères par ultra-rush Ultra-rush venom immunomotherapy induces basophils inhibition by a lower surface expression of FcεRI and leads to early change in innate and adaptive immune response." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR091.

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L'immunothérapie spécifique (ou désensibilisation) aux venins d'hyménoptères est un traitement qui permet de prévenir la récidive d’une anaphylaxie chez les patients allergiques au venin de guêpe ou d’abeille. Une augmentation très rapide des doses est souvent utilisée lors de la phase initiale de ce traitement dont la bonne tolérance n’est pas bien expliquée. Le but de ce travail était de décrire les changements précoces du système immunitaire pendant l’initiation de l’immunothérapie aux venins d’hyménoptères pouvant expliquer cette bonne tolérance. Nous avons inclus 29 patients traités pour une allergie au venin d’hyménoptères avec une initiation de traitement par « ultra-rush » en 3h30. Des prélèvements sanguins ont été pratiqués avant le début du traitement, à 1h30 et juste avant la dernière injection de venin. L’évolution de la tryptase sanguine a été analysée. L'activation des polynucléaires basophiles ainsi que l'expression FcεRI à leur surface ont été analysées par intensité moyenne de fluorescence par cytométrie en flux. Pour évaluer l'évolution de la réactivité des polynucléaires basophiles, un test d'activation des basophiles (TAB) a été réalisé à chaque temps. L’évolution des populations lymphocytaires T et myéloïdes a été également analysée par cytométrie en flux. Nous avons montré une diminution significative de la tryptase sérique pendant l’ultra-rush, de même qu’une diminution significative de l’activation des polynucléaires basophiles et une diminution de l’expression de FcεRI à leur surface. Etonnamment, le TAB a montré une réponse in vitro des basophiles significativement plus élevée à l'extrait de venin à la fin de « l'ultra-rush » par rapport à avant le début du traitement. Nous avons également montré une augmentation significative des cellules dendritiques et une diminution significative des lymphocytes « Natural Killer » (NK) dans le sang. Concernant les populations lymphocytaires T, nous avons montré une ugmentation significative des populations lymphocytaires T dans le sang, sauf pour les Lymphocytes T CD4+et CD8+ naïfs. En conclusion, l’augmentation des doses de venin par « ultra-rush » est bien tolérée grâce à une inhibition des polynucléaires basophiles impliquant une diminution de l’expression de FcεRI à leur surface. L'ultra-rush entraîne également des modifications précoces dans la réponse immunitaire innée et adaptative
Hymenoptera venom immunotherapy (VIT) is a treatment that prevents sting inducing anaphylaxis in allergic patient. Fast-up dosing schedule are often used at the initial phase of VIT. This fast dosing schedule well tolerated, but the mechanisms behind this good tolerance have not yet been elucidated, as well as its consequences on the rest of the immune systems. The aim of this study is to describe early immune system change during initial phase of VIT We included 29 patients undergoing VIT by 3h30 ultra-rush up dosing phase. Blood puncture was performed before the beginning of the treatment, at 1h30 and just before the last venom injection. Blood tryptase evolution was measured. Basophils phenotype and FcεRI surface expression were analyzed by flow cytometry at each step of the ultra-rush. To assess basophils responsiveness evolution, basophils activation test (BAT) was also perform. Myeloid and T lymphocytes population’s evolution were analyzed by flow cytometry. We have shown a significantly lower concentration of blood tryptase at the end of ultra-rush, and a significantly lower basophils activation and FcεRI expression. Surprisingly, BAT has shown a significantly higher in vitro response to venom extract at the end of ultra-rush. We also found significantly increase in blood dendritic cells concentration and lower blood Natural Killer (NK) Cells. We observed higher lymphocytes population in blood except for naïve CD4+ and CD8+ T cells. In conclusion, ultra-rush fast up dosing is well tolerated thanks to a basophils inhibition involving lower FcεRI surface expression. Ultra-rush also leads to early change in innate and adaptive immune response

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Bonvalet, Mélodie. "Caractérisation et suivi chez l’Homme des réponses lymphocytaires T CD4 périphériques spécifiques d’allergènes, naturelles ou induites lors de traitement par immunothérapie allergénique." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T098/document.

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L’immunothérapie allergénique (ITA) est la seule thérapie capable d’agir sur l’étiologie des allergies. La compréhension des mécanismes d’action de ce traitement et la mise en évidence de biomarqueurs d’efficacité favoriserait l’optimisation de l’ITA. A l’aide des tétramères de classe II, nous avons suivi les lymphocytes T CD4 périphériques spécifiques d’allergènes, acteurs centraux de la réaction allergique, dans des conditions normales, pathologiques ou en cours d’ITA, afin d’établir un lien entre ces trois situations physiologiques. Nous avons mis en évidence des différences entre les réponses lymphocytaires T CD4 spécifiques d’allergènes saisonniers et perannuels, chez les individus sains et allergiques. Puis, lors de 2 études cliniques d’ITA sublinguale, l’une menée chez des adultes allergiques aux pollens de graminées traités pendant 4 mois et l’autre menée chez des enfants allergiques aux acariens traités pendant 1, nous avons respectivement observé une diminution des lymphocytes Th2A et une augmentation de la production d’IFN- γ liées au traitement. Toutefois, ces variations ne corrèlent pas avec l’efficacité clinique de l’ITA observée dans ces deux études. Les limites d’utilisation des tétramères de classe II nous ont amené à rechercher si l’expression de marqueurs d’activation membranaires pouvait remplacer un marquage « tétramère ». Alors qu’une corrélation insuffisante a été observée entre le marquage « tétramère » et l’expression des marqueurs d’activation testés, nous avons mis en évidence 3 populations cellulaires aux propriétés fonctionnelles diverses, soulignant l’hétérogénéité des réponses lymphocytaires spécifiques d’allergènes. De plus, la découverte des lymphocytes Th2A pourrait être une approche prometteuse pour le suivi des réponses lymphocytaires T CD4 spécifiques d’allergènes lors d’ITA à plus long terme
Allergenic immunotherapy (AIT) is currently the only curative treatment for allergic disease. Whereas efficacy of this treatment is well established, its mechanisms of action are not clearly understood and predictive as well as surrogate biomarkers are needed to further support AIT development. We focused on allergen specific CD4 T cells, highly involved in allergic inflammation, and monitored their responses both in normal and pathologic conditions, or during AIT. Using MHC class II tetramers, we highlighted distinct patterns of polarization between seasonal and perennial allergen-specific CD4 T cells as well as between healthy and allergic individuals. Then, allergen-specific CD4 T cell responses were monitored during 2 double-blind placebo-controlled sublingual AIT clinical trials. After short term AIT (4 months), we observed a decrease of Th2A cells, a newly define subset, thought to contain most allergen-specific CD4+ T cells. IFN-γ production was increased after one year of treatment. However, these variations were not related to AIT clinical efficacy. We further compared the expression of various activation markers and MHC class II tetramer staining following in vitro stimulation in order to circumvent inherent limitation of tetramers. No correlation could be established between tetramer staining and the expression of multiple activation markers in allergen-stimulated CD4 T cells. Combining these methods helps understanding patient heterogeneity regarding CD4 T cell responses. Moreover, Th2A cells detection is likely a promising approach to identify allergen-specific CD4 T cell during long-term AIT

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24

Tabbah, Khaldoun. "Specific immunotherapy for perennial allergic rhinitis." Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299414.

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MacKenzie, Karen Joan. "Peptide immunotherapy in models of allergic airways disease." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5911.

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Allergen-reactive CD4+ T cells are implicated in the pathogenesis of allergic disease. Peptide immunotherapy (PIT) involves therapeutic administration of short immunodominant peptides from within the protein allergen to which CD4+ T cell responses are directed. This approach can induce tolerance of allergen-reactive CD4+ T cells, while negating the risk of severe allergic reactions associated with whole allergen specific immunotherapy. PIT therefore holds promise as a diseasemodifying treatment for allergic patients. However, further information regarding the mechanisms of action of PIT are required to aid translation to the allergy clinic. Chicken ovalbumin (OVA) is a commonly used model allergen in mouse models of allergic airways inflammation (AAI). Trackable, T cell receptor transgenic T cells recognizing the immunodominant 323-339 peptide of OVA (pOVA) allow mechanistic investigation of PIT in response to pOVA. This thesis investigated the hypothesis that strong, systemic T cell responses induced by intravenous administration of soluble pOVA will induce i) tolerance to pOVA and ii) linked suppression to any additional OVA T cell epitopes, hence improving OVA-induced AAI. Contrary to the hypothesis, intravenous pOVA PIT did not improve disease in a C57BL/6 model of OVA-induced AAI. Models of OVA-induced allergic sensitisation and AAI were therefore developed incorporating trackable CD4+ pOVA-reactive T cells (OT-II cells). pOVA PIT induced tolerance of these cells in an allergic sensitisation setting, but had limited impact on the overall OVA response. Yet, in a model of AAI driven solely by Th2 polarised CD4+ OT-II cells, pOVA PIT did improve disease. It was concluded that, in non-transgenic C57BL/6 mice, CD4+ T cells responding to additional epitope(s) within OVA were important in driving disease and that these T cells were not subject to linked suppression following pOVA PIT. Using a panel of overlapping peptides constituting the sequence of OVA, a novel CD4+ epitope within OVA was characterised. The effects of PIT using pOVA in combination with a peptide containing this additional epitope on OVA-induced AAI were then assessed. Findings from this project therefore hold importance for future mechanistic work surrounding PIT in allergic disease.

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Denson, Marian. "Rational design of immunotherapy to treat fungal allergy." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/rational-design-of-immunotherapy-to-treat-fungal-allergy(ff331eb5-0b27-4a41-823f-b767f5273508).html.

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Background: Asthma affects 5.4 million people in the UK. Asthma subgroups are also susceptible to inhalation of fungal spores (Aspergillus fumigatus) and development of pulmonary fungal aspergilloma; presenting a life threatening but poorly understood condition. NHS costs for corticosteroids, bronchodilators and antifungal agents that are only partially effective continue to rise. Allergy immunotherapy development is of great interest as it is specific to the allergen and can harness key adaptive immune T-cells to down-regulate inflammatory responses. Immunotherapy has been used with varying degrees of success for treatment of grass, pollen, venom, cat and dog allergens however to date has not been directed to fungal allergens. The study aims were: 1) to further understand the A. fumigatus allergens and the protein epitopes responsible for generating immune responses. 2) To genotype participating ABPA/SAFS patients to observe any HLA associations. Methods: 37 subjects with fungal sensitivity were recruited to the study which received permission from the local ethics committee (UHSM LREC). Computer bioinformatic predictions using Propred software identified several potential fungal T cell peptide epitopes; of which 8 peptides were soluble and tested in vitro for specific T-cell proliferation responses by flow cytometric analysis. Skin prick tests determined subject responses to fungal allergens including A. fumigatus, and DNA analysis determined subject HLA type. Results: 5 of 8 soluble peptides were Aspergillus fumigatus derived and 3 from Alternaria alternata. All 8 peptides induced higher CD4 proliferative responses in ABPA/SAFS patients, compared to healthy controls from highest significance to lowest as follows: peptide 1.1 > 9.1 > 8.1 > 2.1 > 9.1.1 > 4.1 > 4.1.1 and 10.1.1. 73% subjects elicited skin responses to A. fumigatus. DNA HLA typing identified alleles associated with ABPA/SAFS but not all allele sub types. Discussion: The ABPA/SAFS group consistently raised T-cell responses to fungal peptides compared to controls. This demonstrates peripheral CD4s retain memory for fungal specificity and clearly respond when challenged with fungal epitopes in vitro. This concept underpins the rationale to further characterize the responding CD4 cells and pursuing bioinformatics approaches for immunotherapy investigations for fungal allergy.

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Zou, Li-Ping. "Immunoregulation and immunotherapy in experimental autoimmune neuritis /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3918-7/.

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Sharif, Sameena. "Biodegradable microparticles as delivery systems for the allergens of Dermatophagoides pteronyssinus (house dust mite)." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294244.

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Gray, Nicola. "Birch pollen specific immunotherapy (BP-SIT) and the oral allergy syndrome." Thesis, University of Brighton, 2016. https://research.brighton.ac.uk/en/studentTheses/ccbab1b8-1f14-4f2e-af29-28d9a045f41d.

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The major birch allergen Betulae verrucosa 1, (Bet v 1), belongs to the proteinase 10 (PR-10) family of panallergens that are common to many fruits, nuts and vegetables. A high proportion of birch-sensitised individuals experience oral symptoms upon consumption of such foods. This has been termed ‘oral allergy syndrome (OAS),’ or ‘pollen-food syndrome.’ Birch pollen specific immunotherapy (BP-SIT) can successfully treat birchsensitive rhinitis; it has been postulated that BP-SIT might also reduce oral allergy symptoms. Previous studies have been small and contradictory, using differing methodology and primary outcome measures. We designed a placebo controlled, double blind, randomised study aiming to establish definitively whether BP-SIT can effectively treat the pollen-food syndrome; outcome measures include open and double blind placebo controlled food challenges (DBPCFC) after one and two years of treatment. To date 22 patients have been enrolled, 18 have undergone assessment at one year and ten at two years. Four patients are due to attend for final followup in Autumn 2015. Eight patients have dropped out. Of the ten who have completed the study: nine have an increased tolerance to fresh apple as evaluated by open challenge. When assessed with DBPCFC, six patients tolerated larger quantities of fresh apple at two years compared to baseline. However, a total of eight patients were noted to have an apple threshold of 100g or more at baseline, despite reacting to only 20g during screening. The clinical trial is on going and remains blinded; it is therefore impossible to draw any firm conclusions regarding the efficacy of BP-SIT to treat OAS at this time.

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Anagnostou, Aikaterini Katherine. "Peanut oral immunotherapy in children : insights from a clinical trial." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648425.

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Victor, Jefferson Russo. "Mecanismos regulatórios mediados pelos anticorpos maternos na modulação da resposta de hipersensibilidade do tipo I ao alérgeno ovalbumina em camundongos neonatos." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-25032009-171427/.

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Avaliamos os mecanismos regulatórios desencadeados pela imunização materna na resposta alérgica da prole OVA. A imunização materna com OVA promoveu alterações como o aumento da expressão dos receptores FcgRIIb nos linfócitos B esplênicos dos neonatos aos 3 dias de idade (d.i.), o que se manteve até os 20 d.i. Com a imunização das proles no período neonatal a imunização materna inibiu a produção de anticorpos IgE anti-OVA. Além disso, foi observado na população de linfócitos B da prole o aumento da expressão dos receptores FcgRIIb e CD44. A transferência passiva de IgG de mães imunes no pós-natal mostrou uma inibição da produção de IgE, e no período pré-natal foi capaz de reduzir a expressão das moléculas CD40 e CD23 nos linfócitos B e a secreção de IL-10 em linfócitos T CD4 na prole no período neonatal. As evidências mostram que a imunização pré-concepcional com OVA induz mecanismos que regulam a resposta IgE da prole imunizada no período neonatal, o que foi parcialmente observado com a transferência passiva de anticorpos IgG durante o período pré e pós-natal.
To evaluate the regulatory mechanisms triggered by maternal immunization in the immune response of the offspring, the effect of preconceptional immunization with OVA was evaluated. Maternal immunization with OVA led to early alteration with increased expression of FcgRIIb in B lymphocytes from 3 days old pups. Offspring from immune mother showed diminished percentage of CD4 T cells IL-4+. The immunization of offspring during neonatal period showed that maternal immunization inhibits the production of anti-OVA IgE antibodies. The evaluation of CD4 T cell population revealed diminished IL-4+ cells. Passive IgG transfer from immune mother during neonatal period showed inhibition in the IgE synthesis, during pregnancy showed capacity to reduce the expression of CD40 molecules in B cells from neonatal pups. These evidences show that maternal OVA immunization down regulates the IgE response of offspring including phenotypic and functional alteration in B and CD4 T cells. These alterations were partially observed with IgG transfer during pregnancy or after birth.

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Wachholz, Petra Anna Helene. "Investigation of the human T cell response to grass pollen allergens : effects of specific immunotherapy (SIT)." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402572.

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Charlesworth, James. "Regulatory B cells in seasonal allergic rhinitis and the influence of grass pollen immunotherapy." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/29877.

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Introduction: Interleukin (IL)-10-producing B cells (Bregs) regulate immune responses in autoimmune disease; however their role in allergy is unclear. Allergen exposure in predisposed atopic individuals results in the induction of IgE-secreting B cells, crucial in the immunopathophysiology of allergic rhinitis. Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis. AIT results in long-term clinical and immunological tolerance; however, whether Bregs contribute towards AIT-induced tolerance remains unclear. Hypotheses: 1. In vitro induced IL-10-producing B cells regulate allergen-driven Th2 inflammation, 2. Bregs are present in fewer numbers in seasonal grass pollen allergic (SAR) individuals compared with healthy controls, which is restored during AIT. Methods: B cells were isolated and subjected to flow cytometry to detect surface markers and IL-10 capacity following CpG stimulation. FluoroSpot, ELISA or qPCR were used to confirm IL-10. Suppression of T cell proliferation (by CFSE) and cytokine production (by ELISA) were carried out in co-cultures. Regulatory B cells in SAR (n=14), AIT (n=18) and healthy (n=14) donors were compared. Nasal allergen challenge (NAC) was carried out, with blood taken pre and post challenge for flow cytometry. Results: CpG significantly enhanced proportions of Bregs, with enrichment particularly within CD24hiCD27+, CD5hi, PD-L1+ and CD24hiCD38hi populations. Bregs suppressed both polyclonally- and grass pollen allergen-stimulated T cells. Ex vivo, proportions of IL-10+ B cells from SAR and healthy donors matched, but were significantly greater amongst AIT donors (particularly sublingual immunotherapy - SLIT) compared to SAR. Following NAC, proportions of B cells within CD24hiCD38hi, CD5hi, CD24hiCD27hi and CD25+ subsets were significantly increased amongst non-allergic and AIT groups, but not amongst SAR donors. Conclusion: Bregs are capable of suppressing allergen induced, Th2-driven inflammation in vitro and may be involved in the induction of tolerance during allergen immunotherapy in vivo, particularly following SLIT.

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Omar, Shumi. "Patienters skattning av allergiska symtom, medicinering och livskvalitet i samband med allergenspecifik immunterapi." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-339599.

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SAMMANFATTNING Introduktion Olika typer av allergier utgör de vanligaste folksjukdomarna i Sverige. Allergenspecifik immunterapi (ASIT) är en behandlingsmetod för patienter med måttlig till svår allergisk rinit med eller utan astma, då symtomlindrande behandling varit otillräcklig. Syfte Syftet med denna studie var att få ökad kunskap om hur patienter skattar sina allergiska symtom, skattning av egenvårds medicinering samt skattning av den hälsorelaterade livskvaliteten, före, under och efter avslutad ASIT-behandling mot björkpollen och/eller 5-gräs. Metod Studien var en kvantitativ registerstudie med deskriptiv och komparativ ansats. Patienters skattning av allergiska symtom och skattning av egenvårds medicinering samt den skattade livskvaliteten har studerats. Datainsamlingen är gjord under åren 2005 - 2009 med hjälp av ett självskattningsformulär som tilldelades patienter som fick ASIT-behandling på en Lung- och allergimottagning på ett sjukhus i mellan Sverige. Undersökningsgruppen bestod av 42 patienter, 22 män och 20 kvinnor. Medelåldern i gruppen var 34,7 år. Resultat Resultatet i denna studie visade att det finns ett negativt samband mellan patienters skattning av allergiska symtom och skattning av livskvalitet både före och efter avslutad ASIT behandling. Livskvaliteten skattades signifikant högre mellan första och sista mätningen i hela patientgruppen. Både kvinnor och män skattade lägre egenvårds medicinering under behandlingstiden, men resultatet visar inte på några signifikanta skillnader i skattning av medicinering mellan kvinnor och män. Resultatet visade inga skillnader mellan könen avseende förändringen i den skattade livskvaliteten. Slutsats Patienterna skattar mindre allergiska symtom och lägre behov av egenvårds medicinering men högre livskvalitet efter ASIT-behandling. Resultatet visar inga skillnader mellan könen. Sådan kunskap kan bidra till värdefull information till vårdgivaren och det i sin tur kan bidra till en bättre omvårdnad av patienter som erhåller ASIT-behandling.
ABSTRACT Introduction Different types of allergies constitutes one of the public health diseases in Sweden. Allergenspecific immunotherapy (ASIT) is a treatment for patients with moderate to severe allergic rhinitis with or without asthma, where symptomatic treatment was insufficient. Aim The aim of this study was to obtain knowledge about how patients estimate their allergic symptoms, their estimation for self-care medication and their estimation of quality of life before, during and after ending the ASIT-treatment with birch pollen and or 5-grass allergen. Method A descriptive, comparative, quantitative patient journal study was conducted. Patients estimation of their allergy symptoms, their estimation of self-care medication and estimation of quality of life have been studied. The data was collected during the years of 2005-2009 by using self -assessment questionnaires wish was given to patients that was receiving ASIT treatmentat a Lung and Allergy Department, at a hospital in the middle of Sweden. The study group consisted of 42 patients, 22 men and 20 women with a mean age of 34,7 years. Results The main findings of this study shows that there is a negative connection between patient’s estimation of their allergic symptoms and quality of life both before and after ending ASIT treatment. Patients estimation of the quality of life got significantly higher in the whole study group comparing first and last measurement. Both women and men estimated lowered selfcare medication during the treatment period, but no significantly differences could be found between the genders regarding estimation of their medication. The result showed no differences between the genders regarding estimation of quality of life. Conclusion Patients estimated less allergic symptoms and lower need of self-care medication but a higher quality of life after ASIT-treatment. The result shows no differences between genders. Such knowledge can contribute to valuable information to caregivers and in turn it may result in a better care of patients who receives ASIT-treatment.

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Ferro, Karla Priscila Vieira 1981. "Imunoterapia específica = efeitos sobre granulócitos de pacientes alérgicos ao veneno de Apis Mellifera." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309580.

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Orientador: Ricardo de Lima Zollner
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: As reações alérgicas à ferroada de inseto resultam de resposta exacerbada do sistema imune, com produção de elevados níveis de anticorpos IgE alérgeno-específicos e padrão de citocinas Th2, envolvidas na diferenciação de linfócitos B específicos para aquele antígeno em células produtoras de IgE e recrutamento de células efetoras da resposta alérgica. Neste contexto, granulocitos são células efetoras importantes na fase tardia da resposta alérgica e estão envolvidos na patogênese de diferentes doenças. Eosinófilos e neutrófilos, especificamente, modulam a resposta imune por meio de diferentes mecanismos, como a secreçao de citocinas, quimiocinas e mediadores lipídicos. A IgE desempenha papel central na patogênese das doenças alérgicas, interagindo com dois receptores de membranas: alta afinidade FcsRI e baixa afinidade FcsRII (CD23). A ligação da IgE ao seu receptor em mastocitos e basófilos promove a liberação de mediadores inflamatórios, dentre eles, a histamina. A histamina além de induzir os sintomas agudos da reação alérgica, sustenta a reação inflamatória até a fase crônica, sendo estes efeitos mediados através da ativação de diferentes receptores (H1, H2, H3 e H4). Os fatores liberadores de histamina (HRF), particularmente, HRF-dependentes de IgE, induzem a liberação de histamina na fase tardia da resposta alérgica, permitindo a perpetuação dos eventos inflamatórios crônicos. Muitos estudos demonstram a eficácia da imunoterapia específica na dessensibilização e no desenvolvimento de tolerância em indivíduos com quadros graves de hipersensibilidade à ferroada de insetos, sobretudo da classe Hymenoptera. Com base nestas informações, foram objetivos do presente trabalho avaliar os efeitos modulatórios da imunoterapia sobre a expressão gênica dos receptores de histamina (H1, H2 e H4), HRF- IgE dependente e de fatores apoptóticos (Bcl-2 e BID) por RT-PCR, além da expressão gênica, através da técnica de PCR em tempo real de fatores de transcrição envolvidos na diferenciação de granulocitos como PU.1, C/EBPa, C/EBPpe GATA-1, receptores de alta (FcsRla e FcsRly) e baixa afinidade de IgE (CD23), cuja detecção protéica foi realizada por imunofluorescência e citometria de fluxo, respectivamente. Além disso, foram avaliados os níveis séricos de IgE específica, secreçao de RANTES e IL-8 nos sobrenadantes das culturas celulares e quantificação de granulocitos apoptóticos através da técnica de TÚNEL. Os granulocitos foram isolados de pacientes submetidos à imunoterapia específica ao veneno de abelha, em diferentes períodos do tratamento (Pré, 1, 3, 6, 12, 18 e 24 meses), após injeção subcutânea, e submetidas à cultura por 72 horas, com estimulo de 1 ng/mL veneno de abelha. Indivíduos não alérgicos foram estudados como grupo controle. De maneira geral, a imunoterapia específica ao veneno de abelha foi capaz de modular os elementos analisados, reduzindo significativamente a expressão dos mesmos ao final de 24 meses de tratamento. Não verificamos, apenas, modulação no número de granulocitos apoptóticos ao longo da imunoterapia. Nossos resultados inéditos fornecem informações adicionais sobre os efeitos da imunoterapia sobre granulocitos, reforçando as propriedades supressoras e tolerogênicas desta forma de tratamento
Abstract: Allergic reactions to insect stings results from a exacerbated response of the immune system, resulting in the production of high levels of allergen-specific IgE antibodies and Th2 cytokine pattern, which are involved in the differentiation process of B lymphocytes, specific for that antigen, into IgE producing cells and the recruitment of effector cells of allergic response. Eosinophils and neutrophils, specifically, modulate the immune response through different mechanisms, such as the secretion of cytokines, chemokines and lipid mediators. IgE plays a central role on allergic diseases pathogenesis, interacting with two membrane receptors: high affinity FcsRI and low affinity FcsRII (CD23). Biding of IgE with receptors on mast cells and eosinophils promotes the release of inflammatory mediators, among them, histamine. Histamine, besides inducing acute symptoms of allergic reaction, supports inflammatory response until its chronic stage; these effects are mediated through the activation of distinct receptors (H1, H2, H3 and H4). Histamine releasing factors (HRF), particularly, IgE dependent HRF, induce histamine release during the late phase of allergic response, allowing the perpetuation of chronic inflammatory events. In this context, many studies have demonstrated the efficacy of specific immunotherapy on desensitization and tolerance development in subjects with severe hypersensivity to insect stings, especially Hymenoptera. Based on all these information, the aim of the present study were to evaluate the modulating effects of immunotherapy on gene expression of histamine receptors (H1, H2 and H4), IgE dependent HRF and apoptotic factors (Bcl-2 and BID), through RT-PCR; in addition to gene expression, through real time PCR, transcriptional factors involved at granulocytes differentiation as of PU.1, C/EBPa, C/EBPp and GATA-1, and protein expression of high (FcsRIa e FcsRly)and low affinity (CD23) IgE receptors, assessed by immunofluorescence and flow cytometry, respectively. Serum levels of specific IgE were also assessed, along with RANTES and IL-8 secretion in cell culture supernatant and quantification of apoptotic granulocytes through TUNEL technique. Granulocytes were isolated from patients undergoing bee venom specific immunotherapy in different periods of treatment (Pre, 1, 3, 6, 12, 18 and 24 months), after subcutaneous injection, and cultured for 72 hours, with bee venom 1ng/ml_. Non allergic subjects were studied as control group. Overall, bee venom specific immunotherapy was able to modulate the analyzed elements, significantly reducing their expression at the end of 24 months of treatment. Modulation on the number of apoptotic granulocytes were not observed during immunotherapy. Our results provide additional information about the effects of immunotherapy over granulocytes, reinforcing the suppressor and tolerogenic properties of this treatment
Doutorado
Ciencias Basicas
Doutor em Clínica Médica

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Vinot, Pierre-Axel. "Développement de pseudo-particules rétrovirales comme vaccin tolérogène et application dans l'allergie alimentaire." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS268.

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L’incidence croissante des désordres immunitaires a motivé le développement de nouvelles approches permettant l’induction d’une tolérance immunitaire spécifique et maintenue dans le temps. S’inscrivant dans ce cadre, la vaccination tolérogène exploite les propriétés innées du système immunitaire pour rétablir la tolérance en visant spécifiquement les cellules dendritiques et les lymphocytes T régulateurs. Ce concept se confronte néanmoins à certaines limitations dues au besoin d’apporter l’antigène sous une forme particulière ou de manière combinée avec un signal de tolérance. En exploitant les propriétés natives des pseudo-particules dérivées de rétrovirus, nous avons mis au point une plateforme permettant de répondre à ces problématiques propres à la vaccination tolérogène. Par ce travail de thèse, l’objectif fut de démontrer la faisabilité de cette approche, en produisant et caractérisant des VLP exprimant l’ovalbumine au sein de la capside et présentant le CTLA-4 à leur surface. Par une étude fonctionnelle sur les cellules dendritiques et sur des cellules présentant une spécificité réactionnelle pour l’ovalbumine, nous avons démontré les propriétés tolérogènes de ces VLP. Ces propriétés ont par la suite été confirmées dans un modèle d’allergie alimentaire induite à l’ovalbumine chez la souris. Les résultats obtenus montrent pour la première fois que ces VLP tolérogènes permettent le contrôle de l’allergie alimentaire de manière spécifique et à long terme et fournissent la preuve de concept de leur utilisation. Les travaux entrepris permettent d’envisager l’utilisation de ces particules dans d’autres champs d’application et notamment les maladies auto-immunes
The increasing incidence of immune disorders has motivated the development of innovative approaches allowing the induction of a specific and long-lasting immune tolerance. Tolerogenic vaccination stands as one of those new therapies and exploits the innate properties of the immune system to restore tolerance by specifically targeting major players such as dendritic cells and regulatory T cells. Nevertheless, this concept faces certain limitations due to the need to provide the antigen in a particular form or in combination with a tolerance signal. By exploiting the native properties of pseudo-particles derived from retroviruses, we have developed a platform to answer those needs. With this thesis research, the objective was to highlight the feasibility of this approach by producing and characterizing VLPs expressing ovalbumin within the capsid and presenting CTLA-4 molecules on their surface. By functional studies on dendritic cells and on ovalbumin specific T cells, we highlight the tolerogenic properties of these VLPs. These properties were subsequently confirmed in a model of ovalbumin-induced food allergy in mice. The obtained results demonstrate for the first time that these tolerogenic VLPs allow the control of food allergy in a specific and long-lasting manner, thus supporting the proof of concept of their use. Additional work also makes it possible to consider the use of these particles in other fields of application and in particular autoimmune diseases

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Imanaka, Takahiro. "An analysis of factors associated with compliance and dropout of sublingual immunotherapy on Japanese cedar pollinosis patients." Kyoto University, 2019. http://hdl.handle.net/2433/244516.

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Hoffman, Riley. "Combining a helminth infection with BM32 vaccination for the treatment of grass pollen allergy." Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/cmc_theses/2081.

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Allergies are considered atopic diseases, or diseases that cause the immune system to create an abnormal amount of IgE antibodies when the body is exposed to an allergen. Allergies affect many people around the world, however many studies have shown a higher rate of allergy in developed countries when compared to developing countries. This discrepancy is hypothesized to be in part because of a decrease in parasitic infections, which have shown to have a protective effect for autoimmune-type diseases, like allergies. There are not many long-term, effective allergy treatments, however a promising allergen-specific immunotherapy technique uses a vaccine that targets B cell epitopes with the hope of increasing the amount of IgG antibodies as opposed to IgE specific antibodies to decrease the likelihood of an allergic reaction. This paper proposes a study that combines the protective effects of a parasite infection with a helminth infection and a B cell epitope vaccination, an already studied BM32 vaccine, to improve allergy symptoms of those with grass pollen allergy. This combination treatment will aim to decrease the number of symptomatic days, eosinophil count found at a scratch test site, and IgE antibodies found within the blood in grass pollen allergic people during peak grass pollen season.

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Brown, Simon Geoffrey Archer, and simon brown@uwa edu au. "Preventing anaphylaxis to venom of the jack jumper ant (Myrmecia pilosula)." Flinders University. School of Medicine, 2003. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20050707.103356.

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Background: Myrmecia pilosula (the jack jumper ant, JJA) is the principal cause of ant venom anaphylaxis in Australia. Whereas honeybee and wasp venom allergy can be treated by venom immunotherapy (VIT), no such treatment is available for ant sting allergy. In addition, information on the natural history of JJA sting allergy is required to identify those most likely to benefit from immunotherapy. The main objectives of this research were to establish: (i) the prevalence, natural history and determinants of reaction severity for JJA allergy, and; (ii) the efficacy and tolerability of JJA VIT. Methods: A search of the Royal Hobart Hospital (RHH) forensic register, a random telephone survey, and a review of emergency department (ED) presentations were performed. Three hundred eighty-eight JJA allergic volunteers were assessed, including serum venom-specific IgE RAST, and then followed up for accidental stings over a 4-year period. Finally, a randomised double-blind, placebo-controlled, crossover trial of JJA VIT was performed. Laboratory parameters measured during the trial were; leukocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. Findings: The prevalence of JJA sting allergy was 2.7% in the Tasmanian population, compared to 1.4% for honeybee. People aged 35 or older had a greater risk of both sting allergy and hypotensive reactions. Four deaths were identified, all in adults with significant comorbidities. During follow-up, 79 (70%) of 113 accidental jack jumper stings caused systemic reactions. Only prior worst reaction severity predicted the severity of follow-up reactions, with the majority of people experiencing similar or less severe reactions when stung again. Sixty-eight otherwise healthy JJA allergic adult volunteers were enrolled in the clinical trial. Systemic reactions to therapy were recorded in 34% during VIT. Objectively defined systemic reactions to sting challenges arose in 1/35 after VIT (mild self-limiting urticaria only) versus 21/29 in the placebo group. Treatment with oxygen, intravenous adrenaline infusion and volume resuscitation was effective and well tolerated. Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. In the placebo group, only VST and HRT were predictive of sting challenge results. Although IgE RAST, leukocyte SI and IL-4 production, LRT and BAT all correlated well with VST, they did not predict sting challenge outcome. After successful VIT, venom-induced leukocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. Interpretation: VIT is highly effective in prevention of JJA sting anaphylaxis and is likely to be of most benefit to people with a history of severe systemic reactions, which usually occur in people aged over 35. Neurocardiogenic mechanisms &/or direct cardiac effects may be important factors in some anaphylaxis deaths. Systemic reactions to immunotherapy are common and require immediate access to resuscitation facilities. The HRT warrants further investigation as a test for selecting those most likely to benefit from VIT. None of the tests evaluated appear to be reliable markers of successful VIT.

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Yang, Ariana Campos. "Efeito da imunoterapia com Dermatophagoides pteronyssinus na resposta clínica e imunológica ao camarão." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-25092009-172821/.

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Objetivo: O objetivo desse estudo foi avaliar alterações na resposta clínica e imunológica ao camarão após a imunoterapia com Dermatophagoides pteronyssinus. Métodos: Selecionou-se 35 indivíduos alérgicos a Dermatophagoides pteronyssinus (Der p), os quais foram submetidos a testes cutâneos de leitura imediata para ácaros, baratas, camarão, tropomiosina recombinante, além de cão, gato e fungos. A detecção de IgE espcífica in vitro foi feita para o ácaro, camarão, barata americana e para suas tropomiosinas. Em todos, avaliou-se reatividade clínica ao camarão através de provocação oral. Dez pacientes foram alocados para o grupo controle, e 25 foram submetidos à imunoterapia alérgeno específica para o ácaro. Os testes cutâneos e a dosagem de IgE sérica específica foram repetidas após a indução da imunoterapia, e após 1 ano do início. A reatividade clínica ao camarão foi reavaliada no final do estudo pela provocação oral. Resultados: No grupo dos pacientes que foram submetidos à imunoterapia, observamos diminuição na reatividade nos testes cutâneos e dosagem de IgE específica para Der p, camarão e tropomiosina recombinante. Dos 10 pacientes com testes cutâneos positivos para camarão, 4 foram negativos na dosagem após um ano de imunoterapia (p= 0,04). Quanto à dosagem sérica de IgE para camarão, dos 9 positivos no início, 6 ficaram negativos (p= 0,014). Nenhum paciente submetido a imunoterapia desenvolveu nova sensibilização para camarão. Não houve alteração na reatividade clínica ao camarão após imunoterapia. Conclusão: A imunoterapia para Dermatophagoides pteronyssinus foi acompanhada de diminuição da reatividade imunológica para camarão e clinicamente não houve alteração da sensibilidade a camarão
Objective: The objective of this study was to determine changes in clinical and immunological response to shrimp after immunotherapy with Dermatophagoides pteronyssinus. Methods: We studied 35 allergic subjects to Dermatophagoides pteronyssinus (Der p), submitted to skin tests to mites, cockroach, shrimp, recombinant tropomyosin, and dog, cat and fungi. The detection of serum specific IgE was performed to mite, shrimp, and tropomyosin from American cockroach. In all patients, the clinical reactivity to shrimp was assessed through oral challenge. Ten patients were allocated to the control group, and 25 were submitted to immunotherapy for mite. Skin tests and determination of serum specific IgE were repeated after the induction of immunotherapy (3-4 months) and 1 year after of beginning of the treatment. The clinical reactivity to shrimp was assessed again at the end of the study by oral challenge. Results: In the group of patients who were undergoing immunotherapy, we observed decreased reactivity in the skin tests and specific IgE levels to Der p, shrimp and recombinant tropomyosin. Among the 10 patients with positive skin tests to shrimp, 4 were negative when assessed after one year of immunotherapy (p = 0.04). About serum specific IgE to shrimp, from the 9 positive reactors in the beginning of treatment, 6 became negative (p= 0.014). There was no change in clinical reactivity to shrimp after immunotherapy. Conclusion: The immunotherapy for Dermatophagoides pteronyssinus was accompanied by decreased immune reactivity to shrimp and clinically there was no change in sensitivity to shrimp

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Martins, Débora Margarida Moreira. "Clínica médica e cirúrgica em animais de companhia." Master's thesis, Universidade de Évora, 2017. http://hdl.handle.net/10174/21309.

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O presente relatório refere-se a cinco meses de estágio curricular realizado no hospital veterinário CasVet. Numa primeira parte são apresentadas as instalações e descritas as atividades médico-veterinárias realizadas e assistidas, a segunda corresponde a uma revisão bibliográfica referente a dermatite atópica canina e, finalmente, a discussão de um caso clínico. Esta dermatopatia ocorre em animais predispostos geneticamente. Desenvolve-se hipersensibilidade a antigénios ambientais, apresentando prurido intenso. O diagnóstico baseia-se numa boa história pregressa, exame clínico e exclusão de outras dermatopatias pruriginosas, contando com possíveis infeções secundárias. Abordagem sintomatológica, evição alergénica, melhoria da condição cutânea e imunoterapia específica constituem as medidas terapêuticas preconizadas. O caso clínico apresentado refere-se a um cão com esta dermatopatia, associada a infeção secundária e intolerância alimentar, tendo sido realizadas diversas provas para confirmação do diagnóstico e posterior controlo dietético e tratamento sistémico; Abstract: Canine atopic dermatitis This report refers to a five monthcurricular internship developed at the veterinary hospital CasVet. The first part presents the hospital facilities and describes the veterinary medical activities performed and assisted, the second part corresponds to a bibliographical review concerning canine atopic dermatitis and, in the last part, the discussion of a clinical case. This dermatopathy occurs in genetically prone animals. A hypersensitivity to environment antigens arises, thus presenting intense pruritus. The diagnosis is based on a good clinical history, clinical exams and the exclusion of other pruritic skin diseases, counting on possible secondary infections. A symptomatic approach, allergenic avoidance, improvement of the skin condition and specific immunotherapy are the recommended therapeutic measures. The clinical case presented refers to a dog with the aforementioned dermatopathy, associated with a secondary infection and food intolerance. Several tests were performed to confirm the diagnosis and subsequent dietary control and systemic treatment was prescribed.

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Graeter, Christine J. "Longitudinal Study of Attention Deficit Hyperactivity Disorder Subjects in the American Clinical Trial of Enzyme Potentiated Desensitization." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1329494113.

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Siebeneicher, Susanne Verfasser], Stefan [Akademischer Betreuer] [Vieths, Masako [Akademischer Betreuer] Toda, and Theodor [Akademischer Betreuer] Dingermann. "Epicutanoeus immunotherapy as a novel prophylactic and therapeutic strategy for birch pollen allergy / Susanne Siebeneicher. Gutachter: Theodor Dingermann ; Stefan Vieths. Betreuer: Stefan Vieths ; Masako Toda." Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2014. http://d-nb.info/1062604075/34.

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Siebeneicher, Susanne [Verfasser], Stefan [Akademischer Betreuer] Vieths, Masako [Akademischer Betreuer] Toda, and Theodor [Akademischer Betreuer] Dingermann. "Epicutanoeus immunotherapy as a novel prophylactic and therapeutic strategy for birch pollen allergy / Susanne Siebeneicher. Gutachter: Theodor Dingermann ; Stefan Vieths. Betreuer: Stefan Vieths ; Masako Toda." Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2014. http://d-nb.info/1062604075/34.

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Queirós, Meimei Guimarães Junqueira de. "Eficácia clínica e alterações na resposta de anticorpos sistêmicos e de mucosa após imunoterapia sublingual em crianças alérgicas a ácaros: um estudo randomizado duplo-cego, controlado com placebo." Universidade Federal de Uberlândia, 2011. https://repositorio.ufu.br/handle/123456789/16569.

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This study aimed to evaluate the clinical efficacy and systemic/mucosal antibody response changes after sublingual immunotherapy (SLIT) using Dermatophagoides pteronyssinus (Dpt) allergens with or without bacterial extracts in mite-allergic children. One-hundred and two patients presenting allergic rhinitis with or without asthma were selected for a randomized double-blind, placebo-controlled trial and distributed into three groups: DPT (Dpt allergen extract, n=34), DPT+MRB (Dpt allergen plus mixed respiratory bacterial extracts, n=36), and Placebo (n=32). Clinical evaluation and immunological analyses were carried out before and after 12 and 18 months of treatment, including rhinitis/asthma symptom and medication scores, skin prick test (SPT) to Dpt extract, and measurements of Dpt, Der p 1, Der p 2 specific IgE, IgG4, and IgG1 in serum and specific IgA in saliva and nasal lavage fluid. Clinical results showed a significant decline in rhinitis/asthma symptom scores in all groups, but medication use decreased only in DPT group after 12 months. SPT results showed no significant changes and SLIT was generally safe, with no severe systemic reactions. SLIT using Dpt allergen alone induced increased serum IgG4 levels to Dpt, Der p 1 and Der p 2, and increased serum IgG1 and salivary IgA levels to Dpt and Der p 1. SLIT using DPT+MRB was able to decrease IgE levels to Der p 2, to increase salivary IgA levels to Der p 1, but had no changes on specific IgG4 and IgG1 levels. In conclusion, clinical improvement was observed both in the SLIT group and the control, but only active SLIT was able to modulate the mucosal/systemic antibody responses. These findings support the role of specific serum IgG4 and IgG1, in addition to salivary IgA, as probable blocking antibodies or biomarkers of tolerance that may be useful for monitoring the allergen specific immunotherapy.
Este estudo teve como objetivo avaliar a eficácia clínica e alterações da resposta de anticorpos sistêmicos e de mucosa após a imunoterapia sublingual (SLIT), utilizando alérgenos de Dermatophagoides pteronyssinus (Dpt), com ou sem extratos bacterianos em crianças alérgicas a ácaros. Cento e dois pacientes com rinite alérgica com ou sem asma foram selecionados para um estudo randomizado duplocego, controlado por placebo e distribuídos em três grupos: DPT (extrato alergênico de Dpt, n=34), DPT+MRB (extrato alergênico de Dpt associado com extrato de bactérias mistas do trato respiratório, n=36), e Placebo (n=32). Avaliação clínica e análises imunológicas foram realizadas antes do tratamento e após 12 e 18 meses, incluindo a pontuação de escores de sintomas e medicamentos de rinite/asma, teste cutâneo (SPT) ao extrato Dpt, e medidas de anticorpos específicos IgE, IgG4 e IgG1 para Dpt, Der p 1, Der p 2 no soro e IgA específicos na saliva e no lavado nasal. Os resultados clínicos mostraram uma redução significativa nos escores de sintomas de rinite/asma em todos os grupos, mas o uso de medicamentos diminuiu apenas no grupo DPT após 12 meses. Resultados de SPT não mostraram mudanças significativas e SLIT foi geralmente segura, sem reação sistêmica grave. SLIT usando somente alérgeno Dpt induziu aumento dos níveis de IgG4 para Dpt, Der p 1 e Der p 2 no soro, e aumentou os níveis de IgG1 no soro e salivares de IgA para Dpt e Der p 1. SLIT usando DPT+MRB foi capaz de diminuir os níveis de IgE para Der p 2, aumentar os níveis salivares de IgA para Der p 1, mas não tiveram alterações nos níveis de anticorpos específicos de IgG4 e IgG1. Em conclusão, foi observado melhora clínica tanto no grupo da SLIT como do controle, porém somente na SLIT com alérgeno foi capaz de modular as respostas de anticorpos sistêmicos e de mucosa. Estes achados reforçam o papel de anticorpos IgG4 e IgG1 séricos específicos, além de IgA salivar, como prováveis anticorpos bloqueadores ou biomarcadores de tolerância que podem ser úteis para monitoramento da imunoterapia alérgeno-específica.
Doutor em Imunologia e Parasitologia Aplicadas

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Rico, Ana Sofia Moreira Vaz. "Os testes de provocação conjuntival na avaliação da eficácia da imunoterapia alergénio-específica rush na dermatite atópica canina." Master's thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2014. http://hdl.handle.net/10400.5/7004.

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Dissertação de Mestrado Integrado em Medicina Veterinária
A atopia é uma doença frequente no cão, mas pouco se sabe acerca do envolvimento ocular, desconhecendo-se a prevalência e o impacto da conjuntivite alérgica (CA) na dermatite atópica canina (DAc). O teste de provocação conjuntival (TPC) é um modelo útil ao seu estudo, sendo utilizado na avaliação da eficácia de várias formas de tratamento, incluindo a imunoterapia alergénio-específica (ITAE). Através da realização de TPC em pacientes atópicos com sensibilização a Dermatophagoides farinae (Df) pretendeu-se avaliar a contribuição deste alergénio nas manifestações oculares e a eficácia da imunoterapia alergénio específica rush (ITAEr) na remissão dos sinais oculares e cutâneos. Foram incluídos no estudo 15 pacientes (n=15) com diagnóstico de DAc e sinais compatíveis com CA. Numa primeira fase todos os animais foram submetidos a TPC para Df e avaliados quanto ao prurido e quanto à gravidade das lesões dermatológicas através do Canine Atopic Dermatitis Extend and Severity Index (CADESI-03). O TPC foi realizado com doses crescentes do alergénio (0.08, 0.4 e 2 BU/mL) até ao aparecimento de um score positivo (≥6), dado pelo somatório das classificações de hiperémia conjuntival, quemose, epífora e prurido ocular avaliadas de 0 a 3 consoante a sua gravidade (ausente, suave, moderado ou grave, respectivamente). Ao prurido foi permitido um grau adicional de 4 (muito grave). O alergénio foi instilado no olho direito (olho teste) e o olho esquerdo serviu de controlo. O teste foi considerado inválido sempre que o olho controlo apresentou uma pontuação ≥6. Na segunda fase do estudo, 2 meses após o início da ITAE rush (ITAEr), os pacientes foram sujeitos a novo TPC e os seus CADESI-03 e escala de prurido reavaliados. Os animais não fizeram qualquer tipo de tratamento, que não a ITAEr, durante o período que decorreu entre fases. As classificações finais relativas aos TPC, prurido e CADESI-03 foram posteriormente comparadas pelo teste de Wilcoxon para amostras emparelhadas (p <0.005). Após a ITAEr, os scores oculares finais foram mais baixos em 87% dos pacientes e 3 animais (20%) apresentaram um TPC negativo. Os valores do CADESI-03 e TPC alteraram-se de 122.80 ± 55.11 e 6.73 ± 0.76 para 97.67 ± 43.95 (p <0.005) e 5.40 ± 1.12 (p <0.002), respectivamente. O prurido decresceu de 8.80 ± 0.86 para 5.70 ± 2.09 (p <0.001). O TPC permitiu estabelecer uma nítida relação entre a afecção conjuntival e a exposição a alergénios para os quais se sabe existir sensibilização, concluindo-se que pode ser útil na avaliação da eficácia da ITAE. A ITAEr pode beneficiar cães atópicos com CA associada, uma vez que a maioria dos animais demonstrou uma resolução parcial ou total sintomatologia ocular e cutânea.
ABSTRACT - EFFECTIVENESS OF RUSH IMMUNOTHERAPY IN ATOPIC DOGS AS ASSESSED BY CONJUCTIVAL PROVOCATION TESTS - Canine atopic dermatitis (cAD) is frequent in dogs, but little is known about eye involvement and the true prevalence and impact of canine allergic conjunctivitis (AC) is still unknown. The conjunctival provocation test (CPT) is used in human to study the ocular response to allergenic stimuli and to evaluate anti-allergic therapy, including specific immunotherapy. The aims of this study are to evaluate the clinical use of the CPT in atopic dogs as a mean of testing the efficacy of rush specific immunotherapy (rSIT) and to understand if this form of treatment is of benefit in canine atopic patients that suffer from AC. 15 dogs with cAD known to be sensitized to Dermatophagoides farinae (Df) that had history of allergic ocular findings and scored positive on the CPT on initial presentation were enrolled in the study. Pruritus was assessed and dermatological sings were graded using Canine Atopic Dermatitis Extend and Severity Index (CADESI-03). Patients were challenged with increasing doses of specific allergen (0.08, 0.4 e 2 BU/mL) until a positive score was reached (≥6). Concerning CPT allergic ocular findings, four criteria (conjunctival hyperemia, epifora, chemosis and pruritus) were scored on a three or four–point scale, separately for each eye. Patients were tested in the right eye before they began rSIT and two months later. The left eye served as control. No other treatment protocol was established for these patients apart from the vaccine administration. In the end CPT, CADESI-03 and pruritus initial and final scores were compared using Wilcoxon test for paired samples (p <0.005). After rSIT, 87% of the patients scored lower on the CPT and 3 animals (20%) showed no response. CADESI-03 and CPT scores decreased from 122.80 ± 55.11 and 6.73 ± 0.76 to 97.67 ± 43.95 (p <0.005) and 5.40 ± 1.12 (p <0.002), respectively. Mean pruritus was significantly lower (8.80 ± 0.86 to 5.70 ± 2.09, p <0.001). With CPT a link can be made between conjunctival pathology and exposure to allergens for which the patient is known to be sensitized. We have demonstrated that CPT can be used to monitor the clinical response of patients to rSIT and that atopic patients with ocular signs benefit from this specific treatment, since the majority showed partial or complete resolution of allergic ocular signs. It is therefore considered that rSIT is of benefit in canine atopic patients that suffer from AC.

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Röver, Anne Constanze. "Phänotypische und funktionelle Charakterisierung peripherer B-Zellen während Wespengiftimmuntherapie." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2001. http://dx.doi.org/10.18452/14646.

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Die Wespengiftallergie stellt eine typische allergische Sofortreaktion dar. Für diese IgE-vermittelten, pathologischen Immunreaktionen ist die spezifische Immuntherapie (IT) die einzige zur Zeit zur Verfügung stehende kausale Therapie. Die Wirkmechanismen sind trotz intensiver Bemühungen weiterhin nicht vollständig aufgeklärt. Als wichtigste These wird zur Zeit eine Verlagerung des pathologischen, TH2-dominierten Zytokinmilieus in Richtung "normales" TH1-Milieu diskutiert. Es wurde auch eine reduzierte Mediatorfreisetzung von Effektorzellen, eine verminderte Leukozytenproliferation, eine verminderte Endorganantwort und charakteristische Ig-Titer-Veränderungen mit initialem Anstieg und längerfristigem Abfall des sIgE und Anstieg des sIgG4 beschrieben. In der vorliegenden Arbeit wurde der Einfluß der IT auf periphere B-Zellen hinsichtlich ihrer Ig-Produktion und ihres Phänotyps untersucht. 15 Patienten mit systemischen Reaktionen nach Wespenstich, Nachweis von spezifischem IgE und positivem Hauttest, bei denen eine Schnell-Immuntherapie eingeleitet wurde, wurden vor Beginn der Therapie (Tag 1), am Tag ihrer Entlassung (Tag 6), also einen Tag, nachdem die Erhaltungsdosis von 100 µg erreicht wurde, und vor der 2. ambulanten Allergeninjektion am 26. Tag untersucht. Die Expression von CD5, CD23, CD32, CD40, CD54, CD86, CD95, HLA-I-ABC und HLA-II-DR wurde auf peripheren mononukleären Blutzellen durchflußzytometrisch bestimmt. Anti-CD19 FITC wurde als spezifischer B-Zellmarker benutzt. Die Serum-Titer des Gesamt-IgE, Wespengift-spezifischen IgE und Wespengift-spezifischen IgG4 wurden mittels ELISA bestimmt. Zur statistischen Auswertung wurde der Wilcoxontest für nicht-parametrische, verbundene Daten benutzt. Die Expression von CD54, CD5, CD32 und HLA-II-DR wurde durch die IT signifikant und die von CD23 tendentiell modifiziert. So war die Expression dieser Moleküle auf der Oberfläche peripherer B-Zellen am Tag 6 im Vergleich zum Ausgangswert vom Tag 1 reduziert. Am 26. Tag wurden wieder Werte auf der Höhe der Ausgangswerte vom Tag 1 gemessen. Dagegen veränderte sich die Expression von CD40, CD86, CD95 und HLA-I-ABC während der untersuchten Zeitpunkte nicht. Die Ig-Titer veränderten sich in der für die IT charakteristischen Weise. So stieg nach 3 Wochen der Gesamt-IgE-, sIgE- und sIgG4-Titer hochsignifikant an. Die Expression der untersuchten Oberflächenmoleküle ist als Indikator für Veränderungen der Aktivationslage und des funktionellen Status der Zellen während der IT zu interpretieren. So spricht die Reduktion der Expression von CD32, CD54 und HLA-II für eine verminderte Aktivierungslage der peripheren B-Zellen. Ferner deutet die Reduktion von CD5 und CD32 auf eine Anergie der B-Zellen hin. Durch die reduzierte Expression von CD23 und CD54 könnte die T-B-Zell-Interaktion verschlechtert werden, die für die Effektorfunktionen beider Zellen bedeutsam ist.Einen wesentlichen Beitrag zur Wirksamkeit der IT könnte auch die verminderte Expression des HLA-II leisten, da HLA-II für die Ag-Präsentation essentiell ist. In dieser Arbeit wurde gezeigt, daß die spezifische Immuntherapie einen Einfluß nicht nur auf die Ig-Produktion der B-Zellen hat, sondern auch auf deren Phänotyp. Dies könnte Hinweise auf bisher nicht bekannte Mechanismen bieten, die an der Wirksamkeit der IT beteiligt sind.
Wasp-venom allergy is a typical IgE-mediated allergic reaction. Specific immunotherapy (IT) is the only currently available causal therapy for IgE-mediated allergies. The mechanisms responsible for the efficacy of IT are still not fully understood. So far, the main focus of research has been on changes of T-helper cell (TH) cytokine production with a shift from TH2 to TH1 cytokines. Reduced mediator secretion from effector cells of allergic reactions, decreased leukocyte proliferation, lowered responsiveness of end organs and changes in immunoglobulin levels have been reported as well. The purpose of this study was to investigate the influence of IT on phenotype and Ig-production of B-lymphocytes. 15 venom allergic patients with a history of systemic reactions after a wasp sting and venom-specific skin test reactivity as well as serum IgE were investigated before VIT (day 1), one day after reaching maintenance dose of 100 µg (day 6) during inpatient rush VIT, and again on day 26 during continued outpatient maintenance therapy. Changes in the serum levels of total IgE, allergen-specific IgE (sIgE) and sIgG4 were measured by ELISA. Expression of CD5, CD23, CD32, CD40, CD54, CD86, CD95, HLA-I-ABC and HLA-II-DR on double labeled B cells was studied by flow cytometry of peripheral blood mononuclear cells. On day 6, cell surface expression of CD54, CD5, CD32 and HLA-II-DR was decreased significantly in intensity and numbers of positive cells, compared to day 1, while on day 26, expression of these molecules approached again baseline levels. Furthermore, a trend to decreased CD23 was noted on day 6. No changes were observed for CD40, CD86, CD95 and HLA-I-ABC. Levels of total IgE, sIgE and sIgG4 showed a significant increase after 26 days of VIT. These data show that initiation of rush VIT has profound effects on B-cell phenotype and Ig-production. Reduced expression of surface molecules can be interpreted as a reduction of activation status of B-cells as well as reduced ability to present antigen and to costimulate other leukocytes. B cells may thus be additional direct or indirect targets of high dose antigen therapy and contribute to the efficacy of IT.

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Vázquez, Ortiz Marta. "Eficacia, seguridad y parámetros predictivos de eventos adversos del tratamiento de inmunoterapia oral en niños alérgicos a proteínas de huevo y leche de vaca. Evolución de parámetros inmunológicos humorales a lo largo del seguimiento." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/134696.

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INTRODUCCIÓN La inmunoterapia oral (ITO) es un tratamiento experimental prometedor para alergia alimentaria, que es una enfermedad prevalente que afecta la salud y la calidad de vida. OBJETIVOS 1. Evaluar eficacia y seguridad de ITO en niños alérgicos a huevo y leche de vaca de 5 a 18 años. 2. Definir fenotipos clínicos de acuerdo al perfil de seguridad observado durante ITO. 3. Analizar la utilidad de los parámetros clínicos e inmunológicos basales para predecir el resultado de seguridad de ITO. 4. Estudiar los parámetros inmunológicos humorales a lo largo del seguimiento, así como su correlación con el perfil de seguridad del tratamiento . MÉTODOS Sujetos: Pacientes de 5 a 18 años afectos de alergia alimentaria mediada por inmunoglobulina E (IgE) a huevo (n= 50) y leche (n= 80) Procedimientos: 1. Determinación basal de parámetros clínicos e inmunológicos. 2. Aplicación de protocolo de ITO a huevo o leche. RESULTADOS 1. Eficacia y seguridad La ITO permitió lograr desensibilización completa en el 73% de alérgicos a leche y en el 54% de alérgicos a huevo. La mayoría de pacientes presentó reacciones adversas por ITO (95% por leche y 90% por huevo). La frecuencia de reacciones fue baja en relación a las dosis administradas (6.6% para leche y 7.6% para huevo) en una mediana de seguimiento de 25 y 18 meses, respectivamente. La mayoría de reacciones fueron leves (grados 1-2). 2. Fenotipos de pacientes de acuerdo al perfil de seguridad de ITO Se identificaron 3 fenotipos: a) Los pacientes cuyas reacciones por ITO cedieron a lo largo del seguimiento, presentaron reacciones infrecuentes y generalmente leves, habiendo logrado desensibilización completa (75% de casos en ITO a leche, 48% en ITO a huevo). En ellos, la ITO se consideró segura y eficaz; b) Los pacientes cuyas reacciones no cedieron durante el seguimiento, presentaron reacciones más frecuentes y más graves, y en su mayoría no habían logrado desensibilización completa (17.5% de casos para leche, 34% para huevo); c) En ITO a huevo, un 18% de pacientes fracasó precozmente por reacciones muy frecuentes y más graves. 3. Utilidad de los parámetros clínicos e inmunológicos basales para predecir la seguridad de ITO a. Los casos de fracaso precoz de ITO a huevo, respecto a quienes pudieron progresar, presentaban niveles basales más elevados de IgE, IgA e IgG4 específicas, formas más graves de asma, así como reacciones más graves y dosis umbrales menores en la prueba de exposición basal. b. Determinados parámetros basales resultaron útiles para predecir la frecuencia, gravedad y persistencia de reacciones en el tiempo: - La IgE específica se correlacionan con la frecuencia, gravedad y persistencia de reacciones. - El prick test se correlaciona con la frecuencia de reacciones y es un factor de riesgo independiente para presentar reacciones grado 4 y más persistentes por ITO a leche. - Reacciones más graves en la prueba de exposición basal se correlacionan con la frecuencia de reacciones y son un factor de riesgo independiente para presentar reacciones más persistentes. - Dosis umbrales más bajas en la prueba de exposición basal se correlacionan con la frecuencia, gravedad y persistencia de reacciones por ITO a leche. - Asma de base más grave se asocia con presentar reacciones grado 4. c. La IgE específica tiene buena rentabilidad diagnóstica para predecir una ITO segura. El punto de corte óptimo para seleccionar pacientes para ITO a leche es IgE específica a caseína inferior a 76.35 kU/L y para ITO a huevo, OVA-sIgE inferior a 6.49 kU/L, que asocian una probabilidad de ITO segura del 93.5% y 79% respectivamente. 4. Evolución de parámetros inmunológicos La IgA específica sérica no se modificó tras 12 meses de ITO a huevo. Prick test e IgE específica disminuyeron tras ITO, mientras que sIgG4 aumentó. Los cambios inmunológicos citados ocurrieron tanto en los niños tratados cuyas reacciones cedieron con el tiempo, como en aquellos que continuaron presentando reacciones durante todo el seguimiento. CONCLUSIONES La ITO permite lograr desensibilización en una amplia proporción de pacientes de 5 a 18 años alérgicos a huevo y leche. Las reacciones adversas por dosis de ITO son comunes. Determinados parámetros clínicos e inmunológicos basales, especialmente la IgE específica, ayudan a identificar los pacientes con alta probabilidad de completar la ITO de forma segura, así como aquéllos que fracasarán precozmente o tendrán reacciones persistentes, frecuentes y más graves. La IgA específica sérica no se modifica tras el tratamiento, mientras que la IgE desciende y la IgG4 aumenta. Los cambios inmunológicos citados no se correlacionan con el perfil de seguridad del tratamiento.
BACKGROUND Oral immunotherapy (OIT) is a promising experimental treatment for food allergy. AIMS 1. To evaluate the efficacy and safety of OIT in cow´s milk (CM) and egg allergic children. 2. To define clinical phenotypes according to the OIT safety profile. 3. To analyze the usefulness of baseline clinical and immune parameters to predict OIT safety. 4. To evaluate the evolution of humoral immune parameters and its correlation with safety phenotypes. METHODS Patients aged 5-18 years diagnosed with IgE-mediated CM and egg allergy (N= 80 and 50, respectively). Determination of baseline parameters. OIT protocol implementation. RESULTS 1. Complete desensitization was reached in 73% of CM-OIT and 54% of egg-OIT patients. Most cases experienced OIT-related reactions, which were mainly mild. 2. Three clinical phenotypes were identified based on OIT safety: a) Children whose reactions resolved over time on-OIT experienced infrequent and mainly mild reactions. Most of them had reached complete desensitization. In them, OIT was safe and effective (75% of cases in CM-OIT and 48% in egg-OIT); b) Children who experienced ongoing reactions over the entire period on-OIT had frequent and mainly moderate reactions (17.5% in CM-OIT and 34% in egg-OIT); c) In egg-OIT, 18% of cases required early discontinuation due to frequent and more severe reactions not improved by medication and protocol re-adaptation. 3. Particular baseline parameters were useful to predict OIT safety. Early discontinuation was associated with higher specific IgE, IgG4 and IgA levels, more severe asthma, lower threshold and more severe reactions at baseline challenge. Specific IgE and lower CM threshold correlated with reactions frequency, severity and persistence. Specific IgE showed good diagnostic performance to predict a safe OIT (optimal cut-offs: casein-IgE < 76 kU/L for CM-OIT, ovalbumin-IgE <6.49 kU/L for egg-OIT). Prick test correlated with reactions frequency and it was an independent risk factor for persistent and grade 4 reactions to CM-OIT. More severe asthma is associated to grade 4 reactions to OIT. More severe reactions at baseline challenge correlate with reactions frequency and they are an independent risk factor for persistent reactions. 4. Serum specific IgA remained unmodified after egg-OIT. Specific IgG4 increased, whereas IgE and prick test decreased after OIT, both in children with ongoing and resolved reactions. CONCLUSIONS OIT induced desensitization in a wide proportion of CM and egg-allergic patients. Reactions were common. Baseline parameters, specially specific IgE, may help identify those patients in whom OIT is more likely to be safe. Changes in humoral immune parameters did not correlate with OIT safety phenotype.

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Rodrigues, Adriana Teixeira. "Produção local de IgE e outros mediadores imunológicos no lavado nasal dos pacientes com rinite alérgica antes e após a realização de imunoterapia específica com o ácaro Dermatophagoides pteronyssinus." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-09082016-144143/.

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A rinite alérgica (RA) é a mais comum doença mediada por IgE, que afeta aproximadamente 500 milhões de pessoas em todo o mundo. A RA é a expressão clínica da ligação entre anticorpos do tipo IgE e antígenos na mucosa nasal resultando em inflamação. Estes anticorpos foram detectados na secreção nasal de pacientes com rinite alérgica. Na abordagem da doença, temos a imunoterapia específica (IT) como único tratamento imunomodulatório antígeno específico. Foi demonstrado que IT gera uma diminuição da resposta tardia ao alérgeno tanto na pele como na mucosa do trato respiratório e esta redução se correlaciona com diminuição no número de células infiltrando os tecidos e na quantidade de mediadores inflamatórios. Objetivo: Determinar a resposta local de IgE específica e IgG4 específica no lavado nasal de pacientes com rinite alérgica antes e após o tratamento com imunoterapia alérgeno específica para Dermatophagoides pteronyssinus por um período de 6 meses; determinar a resposta inflamatória padrão Th1/ Th2/ Th17 e avaliar escore de sintomas e contagem de células no lavado nasal. Método: Selecionamos pacientes sensibilizados ao Dermatophagoides pteronissinus com diagnóstico de rinite alérgica persistente. Realizamos as analises de sintomas nasais através da escala NIS e antes de iniciar o tratamento estes indivíduos realizaram provocação nasal com alérgeno e coleta de lavado nasal. Após 6 meses de tratamento IT e placebo estes pacientes foram reavaliados. Realizamos a analise de Imunoglobulinas (IgE especifica para Der p1 e 2, IgE total, e IgG4 especifica para Der p 1), contagem de células totais, citocinas padrão Th1/Th2 e Th17. Resultados: Analisamos 19 pacientes no grupo imunoterapia e 17 no grupo placebo. A avaliação dos sintomas pela escala NIS após 6 meses de intervenção, demonstrou diferença significativa nos grupos placebo e imunoterapia, em favor da IT. A concentração do extrato utilizado na provocação nasal foi maior no grupo imunoterapia após os 6 meses de tratamento mas sem significância estatística. Quanto a dosagem das imunoglobulinas observamos diminuição da IgE total após a intervenção assim como da contagem de células totais no lavado nasal. A dosagem das citocinas livres no lavado nasal não sofreram alterações significativas. Na provocação nasal observamos aumento de IL-13, IL-10 em ambos os grupos, independente da fase de tratamento. Conclusão: Não observamos nenhuma resposta local de IgE específica e IgG4 específica no lavado nasal de pacientes com rinite alérgica antes e após o tratamento com imunoterapia alérgeno específica para Dermatophagoides pteronyssinus por um período de 6 meses. Houve melhora no escore de sintomas e diminuição da IgE total e da contagem de células no lavado nasal
Allergic rhinitis (AR) is the most common disease mediated by IgE, affecting approximately 500 million people worldwide. The AR is the clinical expression of the link between the IgE-antibodies and antigens in the nasal mucosa resulting in inflammation. Such antibodies were detected in nasal secretions of allergic rhinitis patients. As treatment for this morbidity there is specific immunotherapy (IT) as only immunomodulatory specific antigen approach. It was demonstrated that IT generates a decrease in the late response to the allergen both in the skin and in the mucosa of the respiratory tract and this reduction correlates with the decrease in the number of infiltrating cells and in the amount of inflammatory mediators. Objective: To determine the local response of specific IgE and IgG4 in nasal lavage fluids of patients with allergic rhinitis before and after treatment with specific allergen immunotherapy to house dust mite for a period of 6 months; determine the standard inflammatory response of Th1 / Th2 / Th17 and evaluate symptom score and cell counts in nasal lavage. Method: We selected patients sensitized to Dermatophagoides pteronissinus diagnosed with persistent allergic rhinitis. Nasal symptoms were assessed by Nasal Index Score, and before treatment, allergen nasal challenge and collection of nasal lavage fluid were performed. After 6 months of treatment or placebo, the patients were reevaluated. IgE specific for Der p 1 and 2, total IgE and IgG4 specific for Der p 1, total cell count were determined as well as Th1 / Th2 and Th17 cytokines. Results: We analyzed 19 patients in the immunotherapy group and 17 in the placebo group. The evaluation of symptoms by NIS scale after 6 months of intervention showed significant differences in favor of the immunotherapy group. The concentration of the extract used in the nasal challenge was higher in the immunotherapy group after 6 months of treatment but without statistical significance. The total IgE decreased after the intervention as well as the total cell count in nasal lavage. The dosage of the free cytokines in nasal lavage fluid did not change significantly. In the nasal provocation we observe an increasing in IL-13 and IL-10 in both treatment groups. Conclusion: We observed no local changes in specific IgG4 or specific IgE response in nasal lavage fluid of patients with allergic rhinitis before and after treatment with specific allergen immunotherapy to house dust mite for a period of 6 months. There was an improvement in symptom scores and a decreased of total IgE and cell counts in nasal lavage

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Alkhateeb, Tuqa. "Development, Expansion and Role of Myeloid-Derived Suppressor Cells in Post-Sepsis Immune Suppression." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etd/3787.

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Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 and miR-181b regulate NFI-A expression via a post-transcriptional regulatory mechanism by recruiting RNA-binding proteins HuR and Ago1 to stabilize NFI-A mRNA, thus increasing its protein levels. Studies in our laboratory also showed that inflammatory mediator S100A9 accumulates in the nucleus in Gr1+CD11b+ myeloid precursors in the later phases of sepsis and is necessary for their expansion and programming into immunosuppressive MDSCs. We demonstrate here that nuclear S100A9 associates with specific transcription factors that activate miR-21 and miR-181b expressions. In our final manuscript, we uncover another layer of the mechanisms of MDSC expansion and programming. We found that long non-coding RNA (lncRNA) Hotairm1 binds to and recruits S100A9 to the nucleus to program Gr1+CD11b+ myeloid precursors into MDSCs in the later phases of sepsis. Together, our results reveal three regulatory layers involving NFI-A, S100A9 and Hotairm1 in the pathway leading to MDSCs development in sepsis and suggest that therapeutically targeting these molecular switches might improve sepsis survival.

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