Dissertations / Theses on the topic 'Glomerulonephritis, IGA'

Background Glomerulonephritis is a major cause of end-stage kidney disease (ESRD) in Africa. There is scanty data on the clinico-pathological characteristics and outcome of the mesangioproliferative glomerulonephritides in Africa, despite the non-IgA subtype being reported as a common cause of nephrotic syndrome. This study will assess the outcome of patients with biopsy proven mesangioproliferative glomerulonephritis (MesPGN) from a single centre in Cape Town, South Africa. Methods The study is designed as 10-year retrospective analysis of patients with biopsy proven MesPGN. The MesPGN patterns were divided into non-IgA MesPGN and IgA nephropathy (IgAN), depending on the predominant type of immune deposit. Univariate cox regression analysis was used to determine factors associated with ESRD. Results Data of 109 patients with renal biopsy-proven MesPGN were included for the period between 2005-2014. The mean age at biopsy was 33.8 ±14.9 years, 53.2% were males, and 39.4% were black Africans. Clinically, 58.7% presented with nephrotic syndrome. On histology 79.8% had non-IgA MesPGN, and 20.2% had IgAN. Compared to the non-IgA group, most patients with IgAN were not treated with immunosuppression (72.7% vs. 40.2%; p=0.006). At the last visit, 10.1% reached ESRD (40.9% vs. 2.3%; p<0.0001) and 30.2% achieved complete remission (9.1% vs. 35.7%; p=0.015) for IgAN and non-IgA MesPGN respectively. The 5-year renal survival for IgAN and non-IgA MesPGN respectively, were: 63.3% vs. 97.6%, log rank p=0.001. Overall, hypertension (p=0.019), not receiving immunosuppression (p=0.046) and having IgAN (p=0.007) were independent predictors of progression to ESRD. Conclusion There is a significantly higher ESRD-free survival of patients with biopsy proven non-IgA MesPGN than IgAN. Whether this is related to the limited use of immunosuppressive therapy in IgAN patients or represents a true nature of the disease still requires further research.

Abstract The aim of this work was to describe the clinical features and clinical course of Henoch-Schönlein purpura (HSP) in a prospective setting, to compare the efficacy of cyclosporine A (CyA) and methylprednisolone (MP) pulses for the treatment of severe HSP nephritis (HSN) and to study the effect of prophylactic prednisone treatment given at disease onset on the long-term outcome. A total of 223 children with newly diagnosed HSP were followed up prospectively for 6 months. Patients with severe HSN also had extrarenal symptoms more frequently during this time. Protein loss via the intestine was more common than previously described, occurring in 3% of the patients. HSN developed in the early course of the disease. The results suggest that weekly urine dipstick tests are indicated for 2 months after HSP onset and individually for over 6 months in cases of HSN or HSP recurrences. Prednisone did not affect the frequency or timing of the appearance of HSN. The efficacy of CyA and MP treatments was evaluated in a trial with a mean follow-up time of 6 years involving 24 paediatric patients (11 CyA, 13 MP), 15 of whom were randomized and 9 were treated according to the given protocol without randomization. Oral CyA was not inferior to intravenous MP pulses and proved to be an efficient, safe steroid-sparing treatment for severe HSN. All the CyA-treated patients achieved remission of nephrotic-range proteinuria within 3 months, while remission was achieved more slowly in the MP group and only in 6/13 (46%) with the initial treatment. There was no difference in the renal biopsy findings two years after initiation of the therapy. The 8-year outcome of HSP was assessed by means of a health questionnaire in 160 (94%) of the 171 former patients in the randomized placebo-controlled prednisone trial and in 138 (81%) with urine analysis and measurement of blood pressure. HSP carried a good prognosis, although skin relapses occurred up to a decade after the initial onset and could be accompanied by late-onset nephritis. Hypertension and/or renal abnormalities were recorded in 13% of the patients, being more frequent in those with an initial occurrence of HSN (OR 4.3, p=0.009, 95% CI 1.4–14.0) and warranting long-term follow-up of HSN patients. Early prednisone treatment did not affect the long-term outcome of HSP and should not be routinely used<br>Tiivistelmä Väitöskirjan tarkoituksena oli kuvata Henoch-Schönleinin purppuran (HSP) oireita ja taudinkulkua, verrata siklosporiini A:n (CyA) ja metyyliprednisolonipulssihoidon (MP-pulssihoidon) tehoa vaikean HSP-nefriitin (HSN) hoidossa ja selvittää taudin alussa annetun prednisonihoidon vaikutusta pitkäaikaisennusteeseen. Taudinkulkua seurattiin prospektiivisesti 6 kuukauden ajan diagnoosista 223 lapsipotilaan aineistossa. Potilailla, joilla oli vaikea HSN, esiintyi myös muita oireita pitempään. Proteiinin menetystä suolistoon esiintyi 3 %:lla, mikä on aiemmin kuvattua yleisempää. HSN ilmaantui taudin alkuvaiheessa. Tutkimustulosten perusteella viikoittainen virtsanäytteiden seuranta riittää 2 kuukauden ajan taudin alusta. Seuranta-aikaa tulee pidentää yksilöllisesti yli 6 kuukauden, jos potilaalla todetaan HSN tai HSP uusiutuu. Prednisonilla ei todettu olevan vaikutusta HSN:n yleisyyteen tai ilmaantumisaikaan. CyA- ja MP-hoitojen tehoa vaikeaan HSN:n seurattiin 24 lapsipotilaan aineistossa (11 CyA, 13 MP) 6 vuoden ajan. Potilaista 15 satunnaistettiin hoitoryhmiin ja 9 hoidettiin tutkimussuunnitelman mukaan ilman satunnaistamista. Suun kautta otettu CyA vaikutti hoidoista tehokkaammalta, sillä kaikilla potilailla nefroottistasoinen valkuaisvirtsaisuus hävisi kolmessa kuukaudessa. MP-hoitoa saaneista vain 6/13 (46 %) pääsi remissioon MP-hoidolla ja hekin CyA-hoidettuja hitaammin. Kaksi vuotta tutkimuksen alusta otettujen munuaisbiopsioiden histologisissa löydöksissä ei ollut eroa ryhmien välillä. Varhaisen kortisonihoidon pitkäaikaisvaikutuksia arvioitiin 8 vuotta lumekontrolloidun prednisonihoitotutkimuksen jälkeen, jolloin aiemman tutkimuksen 171 potilaasta 160 (94 %) vastasi terveyskyselyyn ja 138 (81 %) osallistui virtsa-analyysin ja verenpaineen mittauksen sisältäneeseen seurantatutkimukseen. HSP:n ennuste oli hyvä, vaikka taudin iho-oireet saattoivat uusia jopa 10 vuoden ajan ja taudin uusiutumisen yhteydessä saattoi ilmaantua myöhäinen HSN. Kohonnut verenpaine ja/tai valkuais-/verivirtsaisuus todettiin 13 %:lla. Ne olivat yleisempiä potilailla, joilla oli ollut HSN taudin alkuvaiheessa (OR 4.3, p=0.009, 95 % CI 1.4–14.0). Siten HSN-potilaiden pitkäaikaisseuranta on tarpeen. Varhaisella kortisonihoidolla ei ollut vaikutusta taudin ennusteeseen, minkä vuoksi kortisonia tulee käyttää HSP-potilaiden hoidossa vain harkiten

O Lúpus Eritematoso Sistêmico (LES) é uma doença auto-imune caracterizada pela deposição de imunocomplexos nos tecidos. O clareamento de imunocomplexos está comprometido no LES, contribuindo para a patogênese da nefrite lúpica. Os receptores Fcg (FcgR) participam do clareamento dos imunocomplexos contendo IgG, pois se ligam à porção Fc desta molécula. O FcgRIIa é um receptor que tem dois alelos co-dominantemente expressos, o R131 e o H131, os quais diferem na sua eficiência em se ligar a subclasses de IgG. Células que expressam o homozigoto FcgRIIa-H/H131 são as únicas que se ligam eficientemente a imunocomplexos contendo IgG2, enquanto as que expressam FcgRIIa-R/R131 o fazem de forma menos eficaz. Este polimorfismo tem sido descrito como fator de risco para nefrite lúpica, embora ainda haja controvérsias. O propósito do nosso estudo foi o de analisar, em uma população de nefrite lúpica e em outra de glomerulopatias primárias, a associação entre o genótipo FcgRIIa-R/R131 e a gravidade da doença renal na sua instalação (definida pelo momento da biópsia renal) e ao final do seguimento, bem como possíveis relações com aspectos histológicos renais. A genotipagem do receptor FcgRIIa foi realizada em 76 pacientes com nefrite lúpica e 63 com glomerulopatias primárias através da extração do DNA genômico, seguido de reação de polimerização em cadeia (PCR) e nested PCR, utilizando-se primers específicos. Os pacientes foram avaliados por parâmetros clínicos e laboratoriais. Setenta e um pacientes com nefrite lúpica realizaram biópsia renal, enquanto 5 que já se encontravam em hemodiálise não a realizaram. Pacientes com glomerulonefrite membranoproliferativa, nefropatia da IgA e glomerulonefrite proliferativa mesangial foram agrupados como glomerulopatias proliferativas enquanto os com glomeruloesclerose segmentar e focal, glomerulopatia de lesões mínimas ou glomerulonefrite membranosa foram agrupados como glomerulopatias não proliferativas. O homozigoto FcgRIIa-R/R131 foi mais prevalente no grupo com nefrite lúpica (42,1% de R/R131 e 14,5% de H/H131) em relação ao grupo com glomerulopatias primárias (23,8% de R/R131 e 23,8% de H/H131), dado este estatisticamente significativo (p<0.05). Houve segregação do genótipo FcgRIIa- R/R131 nos pacientes com nefrite lúpica quando comparados aos com glomerulopatias não proliferativas, mas não quando comparados aos com glomerulopatias proliferativas (p<0.05). Não houve diferença na distribuição genotípica do receptor FcgRIIa em relação a classe histológica de nefrite lúpica, tampouco em relação aos que evoluíram ou não para insuficiência renal (Pcr = 1,4mg/dl ao final do seguimento). Um aumento na frequência do genótipo FcgRIIa- R/R131 foi encontrado nos pacientes com nefrite lúpica apresentando níveis mais elevados de FAN (FAN>1/100) e consumo de complemento C3 (p<0,05), mas não naqueles com presença de anticorpos anti-dsDNA ou anti-fosfolípide (p>0,05). Estes achados sugerem que uma distribuição anormal dos genótipos do receptor FcgRIIa com predomínio do homozigoto R/R131 é um fator importante que pode influenciar o desenvolvimento de nefrite lúpica e de glomerulopatias proliferativas. O genótipo FcgRIIa-R/R131 também está relacionado com maior atividade lúpica (FAN>1/100 e consumo de C3) em pacientes brasileiros.<br>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by tissue deposition of immune complexes. Immune complex clearance is impaired in SLE, contributing to the pathogenesis of lupus nephritis. Fcg receptors (FcgR) participate in the clearance of the immune complexes containing immunoglobulin G, because they bind the Fc domain of this molecule. The FcgRIIa receptor has two co dominant alleles, R131 and H131. They differ in their efficiency to bind IgG subclasses. Cells expressing the homozygote FcgRIIa-H/H131 are the only ones, which bind efficiently immune complexes containing IgG2, whereas those expressing FcgRIIa-R/R131 do not. This polymorphism has been described as a risk factor for lupus nephritis. However, reports are still controversial. This study aims to establish the role of FcgRIIa polymorphism in the severity and prognosis of lupus nephritis compared to primary glomerulopathies, and whether it is related to histological findings or not. In 76 patients with lupus nephritis and 63 patients with primary glomerulopathies, genotyping of the FcgRIIa receptor was performed with standard PCR, followed by nested PCR using specific primers. The same patients were assessed according to clinical and laboratory patterns. Seventy-one patients with lupus nephritis underwent biopsy, while five did not since they were already under dialysis. Patients diagnosed as membranoproliferative glomerulonephritis, IgA glomerulonephritis and mesangial proliferative glomerulonephritis were grouped as proliferative glomerulopathies, while those with focal segmental glomerulosclerosis, membranous glomerulonephritis and minimal change disease were grouped as nonproliferative glomerulopathies. The homozygous FcgRIIa-R/R131 was more prevalent in lupus nephritis (42,1% being R/R131 and 14,5% H/H131) than in glomerulopathies (23,8% being R/R131 and 23,8% H/H131). These data were statistically significant (p<0.05). A segregation of the FcgRIIa-R/R131 genotype was found in patients with lupus nephritis compared to nonproliferative glomerulopathies, but not when compared to proliferative glomerulopathies (p<0.05). No relation was found between genotype distribution and histological class or renal insufficiency (end-study serum creatinine = 1.4 mg/dl). The genotype R/R131 was more prevalent in lupus nephritis patients presenting complement 3 (C3) consumption and higher antinuclear factor (ANF) titers, but not in those with antidouble- stranded DNA or antiphospholipid antibodies (p>0.05). We concluded that a skewed distribution of the FcgRIIa genotypes with R/R131 predominance may contribute to the development of lupus nephritis and proliferative glomerulopathy. In Brazilian patients, this polymorphism is also related to more intense lupus activity (ANF > 1/100 and C3 consumption).

Li Kam-tao, Philip.<br>"January 2003."<br>Thesis (M.D.)--Chinese University of Hong Kong, 2003.<br>Includes bibliographical references (p. 252-281).<br>Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.<br>Mode of access: World Wide Web.

Chui Shiu Hon.<br>Thesis (Ph.D.)--Chinese University of Hong Kong, 1990.<br>Bibliography: leaves 144-183.<br>ACKNOWLEDGEMENTS<br>SUMMARY<br>LIST OF ABBREVIATIONS<br>Chapter CHAPTER 1. --- INTRODUCTION --- p.1<br>Chapter 1.1 --- IgA Nephropathy --- p.1<br>Chapter 1.1.1 --- History & Epidemiology --- p.1<br>Chapter 1.1.2 --- Clinical Pathological Features --- p.2<br>Chapter 1.1.3 --- Laboratory Findings --- p.3<br>Chapter 1.1.4 --- Immunopathogenesis --- p.5<br>Chapter 1.2 --- The Role of IgA in the Pathogenesis of IgA Nephropathy --- p.10<br>Chapter 1.2.1 --- Structure of IgA Molecule --- p.10<br>Chapter 1.2.2 --- IgA Biosynthesis and Immune Regulation --- p.23<br>Chapter 1.2.3 --- Biological Role of IgA --- p.26<br>Chapter 1.2.4 --- Circulating Immune Complexes in IgA Nephropathy --- p.27<br>Chapter 1.2.5 --- IgA Subclasses in IgA Nephropathy --- p.32<br>Chapter 1.2.6 --- Light Chain Composition of IgA in IgA Nephropathy --- p.33<br>Chapter 1.3 --- Aim of the Present Study --- p.36<br>Chapter 1.4 --- Design of Experiments --- p.37<br>Chapter CHAPTER 2. --- MATERIALS & METHODS --- p.42<br>Chapter 2.1 --- Materials --- p.42<br>Chapter 2.1.1 --- Patients --- p.42<br>Chapter 2.1.2 --- Controls --- p.43<br>Chapter 2.1.3 --- Additional Specimens --- p.43<br>Chapter 2.1.4 --- Serum Samples --- p.44<br>Chapter 2.1.5 --- Chemicals --- p.44<br>Chapter 2.1.6 --- Immunoglobulins --- p.46<br>Chapter 2.1.7 --- Antisera --- p.47<br>Chapter 2.1.8 --- Solutions and Buffers --- p.48<br>Chapter 2.1.9 --- Apparatus and Equipment --- p.51<br>Chapter 2.2 --- Methods --- p.53<br>Chapter 2.2.1 --- Serum Protein Electrophoresis --- p.53<br>Chapter 2.2.2 --- Immunochemical Techniques --- p.54<br>Chapter 2.2.3 --- Fast Protein Liquid Chromatography (FPLC) for Isolation of Serum IgA --- p.64<br>Chapter CHAPTER 3. --- SERUM PROTEIN ELECTROPHORESIS AND IMMUNOGLOBULIN CONCENTRATIONS --- p.67<br>Chapter 3.1 --- Serum Protein Electrophoresis --- p.67<br>Chapter 3.2 --- Serum Immunoglobulin Concentration --- p.67<br>Chapter 3.3 --- Discussion --- p.70<br>Chapter CHAPTER 4. --- LIGHT CHAIN RATIOS OF INDIVIDUAL IMMUNOGLOBULINS --- p.72<br>Chapter 4.1 --- Enzyme-Linked Immunosorbent Assay for Light Chain Concentrations --- p.72<br>Chapter 4.2 --- Light Chain Ratios of Individual Serum Immunoglobulins in Normal Subjects and in Disease --- p.75<br>Chapter 4.3 --- Discussion --- p.77<br>Chapter CHAPTER 5. --- IN VITRO SYNTHESIS OF IgA WITH LAMBDA LIGHT CHAIN IN IgA NEPHROPATHY --- p.83<br>Chapter 5.1 --- Lymphocyte Culture and In Vitro Immunoglobulin Production --- p.83<br>Chapter 5.2 --- In Vitro Immunoglobulin Production and Predominant Synthesis of IgA with λ Light Chain in IgA Nephropathy --- p.83<br>Chapter 5.3 --- Dicussion --- p.87<br>Chapter CHAPTER 6. --- PURIFICATION OF SERUM IgA BY AFFINITY CHROMATOGRAPHY --- p.90<br>Chapter 6.1 --- Fast Protein Liquid Chromatography --- p.90<br>Chapter 6.2 --- Recovery of Isolated IgA --- p.92<br>Chapter 6.3 --- Purity of Isolated IgA --- p.92<br>Chapter 6.4 --- κ/λ Ratio of IgA Before and After FPLC --- p.96<br>Chapter 6.5 --- Subclass of IgA Before and After FPLC --- p.97<br>Chapter 6.6 --- Discussion --- p.100<br>Chapter CHAPTER 7. --- "ANALYSIS OF CHARGE DISTRIBUTION OF IgA, IgA(κ) AND IgA(λ)" --- p.102<br>Chapter 7.1 --- "Iso-Electric Focusing, Immunoblotting, and Densitometry of Purified IgA for Total IgA, IgA(κ) and IgA (λ)" --- p.102<br>Chapter 7.2 --- "Charge Distribution of Plasma Total IgA, IgA(κ) and IgA(λ)" --- p.103<br>Chapter 7.2.1 --- A/C Ratio of Total IgA --- p.103<br>Chapter 7.2.2 --- A/C Ratio of IgA(κ) --- p.113<br>Chapter 7.2.3 --- A/C Ratio of IgA(λ) --- p.113<br>Chapter 7.3 --- Discussion --- p.129<br>Chapter CHAPTER 8. --- GENERAL DISCUSSION --- p.134<br>REFERENCES --- p.140<br>APPENDICES

To Wah Yuen.<br>Thesis (M.Phil.)--Chinese University of Hong Kong, 1994.<br>Includes bibliographical references (leaves 118-142).<br>Acknowledgements --- p.1<br>Summary --- p.3<br>List of Abbreviations --- p.7<br>Chapter Part I --- Alpha2-HS glycoprotein: Identification and Characterization of the Jacalin Binding Properties --- p.8<br>Chapter Chapter 1 --- Introduction --- p.9<br>Chapter 1.1 --- Jackfruit and jacalin --- p.10<br>Chapter 1.2 --- Biochemical and immunological properties of jacalin --- p.11<br>Chapter 1.2.1 --- Molecular Weight of Jacalin --- p.11<br>Chapter 1.2.2 --- Molecular structure of jacalin --- p.11<br>Chapter 1.2.3 --- Specificity of jacalin to Thomsen-Fredenreich- antigen (T-antigen) --- p.13<br>Chapter 1.2.4 --- The internal repeated sequence in the jacalin --- p.13<br>Chapter 1.2.5 --- Jacalin-Bound Proteins (JBP) --- p.15<br>Chapter 1.2.6 --- Interaction of jacalin to JBP --- p.15<br>Chapter 1.2.7 --- Immunological properties of jacalin --- p.16<br>Chapter 1.3 --- Application of jacalin in medical research --- p.17<br>Chapter 1.4 --- Background knowledge of α2HSG --- p.18<br>Chapter Chapter 2 --- Materials and Methods --- p.20<br>Chapter 2.1 --- Design of experiment --- p.21<br>Chapter 2.2 --- Identification of the Unknown JBP --- p.21<br>Chapter 2.2.1 --- Sera --- p.21<br>Chapter 2.2.2 --- Isolation of JBP by Affinity Chromatography --- p.22<br>Chapter 2.2.3 --- Fast protein liquid chromatography (FPLC) of JBP --- p.22<br>Chapter 2.2.4 --- Affinity chromatography with anti-human IgA column --- p.23<br>Chapter 2.2.5 --- Preparation of non-IgA JBP fraction --- p.24<br>Chapter 2.2.6 --- N-terminal sequencing of the non-IgA JBP fraction --- p.24<br>Chapter 2.2.7 --- SDS-PAGE and immunoblot of gel filtration fractions --- p.25<br>Chapter 2.2.8 --- ELISA of FPLC fractions of JBP --- p.26<br>Chapter 2.2.9 --- Immunochemical analysis --- p.27<br>Chapter 2.3 --- α2HSG: the property of jacalin binding --- p.28<br>Chapter 2.3.1 --- α2HSG -jacalin binding curve and competitive ELISA --- p.28<br>Chapter 2.3.2 --- Purification of jacalin-crude extract (JCE) --- p.28<br>Chapter 2.3.3 --- Characterization of JCE and ASJ --- p.29<br>Chapter 2.3.4 --- Comparison of jacalin from different sources for binding to α2HSG by competitive ELISA --- p.29<br>Chapter Chapter 3 --- Results --- p.31<br>Chapter 3.1 --- Identification of the unknown JBP --- p.32<br>Chapter 3.1.1 --- Isolation and FPLC of JBP --- p.32<br>Chapter 3.1.2 --- Identification of non-IgA JBP by anti-human IgA affinity column --- p.32<br>Chapter 3.1.3 --- Identification of the known JBP in the FPLC fractionated JBP --- p.36<br>Chapter 3.1.4 --- Characterization and confirmation of non-IgA JBP --- p.36<br>Chapter 3.2 --- α2HSG: the property of jacalin binding --- p.42<br>Chapter 3.2.1 --- Characterization of α2HSG-jacalin binding --- p.42<br>Chapter 3.2.2 --- Characterization of the purified jacalin --- p.45<br>Chapter 3.2.3 --- Comparison of different batches of jacalin to interact with α2HSG --- p.45<br>Chapter Chapter 4 --- Discussion --- p.53<br>Chapter Part II --- Jacalin-α2HSG binding: the Clinical Values --- p.57<br>Chapter Chapter 5 --- Introduction --- p.58<br>Chapter Chapter 6 --- Materials and Methods --- p.61<br>Chapter 6.1 --- Preparation of IgA-specific jacalin (ASJ) by IgA-Sepharose 4B affinity column --- p.62<br>Chapter 6.2 --- Preparation of JCE- and ASJ-Sepharose-4B affinity column --- p.62<br>Chapter 6.3 --- Factors affecting the yield of α2HSG --- p.62<br>Chapter 6.4 --- Miscellaneous methods --- p.63<br>Chapter Chapter 7 --- Results and Discussion --- p.65<br>Chapter Part III --- Application of Jacalin for Studying the Pathogenesis of IgA Nephropathy --- p.77<br>Chapter Chapter 8 --- An Overview of IgA Nephropathy --- p.78<br>Chapter 8.1 --- Clinical manifestation of IgA nephropathy --- p.79<br>Chapter 8.2 --- Mesangial deposits in IgAN --- p.80<br>Chapter 8.3 --- Human IgA system --- p.81<br>Chapter 8.4 --- The role of circulating IgA in the pathogenesis of IgA nephropathy --- p.84<br>Chapter 8.5 --- Pathogenesis of primary IgA nephropathy --- p.86<br>Chapter 8.6 --- Interaction between circulatory IgA and fibronectin (FN) in primary IgAN --- p.87<br>Chapter Chapter 9 --- Materials and Methods --- p.90<br>Chapter 9.1 --- Design of experiment --- p.91<br>Chapter 9.2 --- Sera --- p.91<br>Chapter 9.3 --- Analysis of IgAl/IgA ratio in sera and JBP --- p.91<br>Chapter 9.4 --- Purification and Fast protein liquid chromatography (FPLC) of jacalin-bound protein (JBP) --- p.92<br>Chapter 9.5 --- Analysis of FPLC-fractionated JBP --- p.93<br>Chapter 9.5.1 --- ELISA of IgA-containing immune complexes (IgA-IC) --- p.93<br>Chapter 9.5.2 --- "Quantitative ELISA of IgA, K-IgAl, and λ-IgAl" --- p.94<br>Chapter 9.5.3 --- "Measurement of sIgA,dIgA and IgA containing immune complex (IgA-IC)" --- p.95<br>Chapter 9.5.4 --- SDS-PAGE analysis --- p.95<br>Chapter 9.6 --- Statistics --- p.95<br>Chapter Chapter 10 --- Results --- p.96<br>Chapter 10.1 --- IgA1/IgA ratio of serum and JBP --- p.97<br>Chapter 10.2 --- Isolation and FPLC of JBP --- p.97<br>Chapter 10.3 --- SDS-PAGE analysis of FPLC fractionated JBP --- p.97<br>Chapter 10.4 --- ELISA of the FPLC fractionated JBP --- p.99<br>Chapter 10.4.1 --- "Distribution of IgA, secretory IgA (sIgA) and dimeric IgA (dIgA) in the FPLC fractions" --- p.99<br>Chapter 10.4.2 --- Distribution of IgA containing immune complex (IgA-IC) in the FPLC fractions --- p.99<br>Chapter 10.4.3 --- Quantitation of IgA --- p.106<br>Chapter 10.4.4 --- "Quantitation of K-IgAl and λ-IgA1, and determination of k/λ ratio of IgAl" --- p.106<br>Chapter 10.4.5 --- "Quantitation of sIgA,dIgA, and IgA-containing immune complex (IgA-IC)" --- p.109<br>Chapter Chapter 11 --- Discussion --- p.112<br>References --- p.118

This KwaZulu-Natal (KZN) based study investigates hypertension, glomerulonephritides and the rarity of IgA Nephropathy (IgAN) in Africans in association with the Human Leukocyte Antigen (HLA). A retrospective hypertensive study found a positive association with HLA-B40 (P c<0.05) and HLA-B15 (Pc<0.02) in Indians and Africans respectively. No association was found in Whites. A prospective study showed glomerulonephritides to be positively associated with HLA-A33 in Indians (Pc 0.049). No associations were found with glomerulonephritides in Africans and Whites. Combined Race groups show no HLA associations. HLA-A30; HLA-A34; HLA-A29; HLA-B42; HLA-B58; HLA-B70 and HLA-DR11 were extremely significantly higher in Africans compared to Indians and Whites (all P<0.0001). In conclusion, HLA-B40 and I 1LA-B15 are possible disease susceptibility markers in Indian and African hypertensives; HLA-A33 is a possible disease susceptibility marker for glomerulonephritides in Indians and alleles in linkage might be responsible for the rarity of IgAN in Africans but further studies need to be employed.<br>Thesis (M.Med)-University of KwaZulu-Natal, 2007.

Nephrotic syndrome is characterized by proteinuria, hypoproteinemia, edemas and hyperlipidemia. It occurs in primary (e.g. focal segmental glomerulosclerosis, FSGS or minimal change disease, MCD) and in secondary glomerulopathies (e.g. kidney amyloidosis). In primary forms, great attention is paid to the potential genetic background of the disease and due to new molecular genetic methods genes, whose mutations cause different nephropathies (e.g. ACTN4 or INF2) were identified. The aims of presented doctoral thesis were following. Firstly, to continue the mutational analysis of ACTN4 that was described in the author's diploma thesis in other glomerulopathies. Secondly, to implement the mutational analysis of INF2 and subsequently analyse this gene in patients with FSGS/MCD and in patients from special group characterized by positive family history for end stage renal disease (ESRD) in combination with advanced chronic kidney disease (CKD) or already developed ESRD at the time of diagnosis. Thirdly, mutational analysis of NPHS2 and TRPC6 (methods implemented in laboratory earlier) in selected patients from the special group. Finally, expression analyses of genes important for podocyte function or connected with human immune system. This part also verifies the applicability of NPHS2/SYNPO expression...