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1

Yamanaka, Kei-ichi, Nikhil Yawalkar, David A. Jones, Daniel Hurwitz, Katalin Ferenczi, Sara Eapen, and Thomas S. Kupper. "Decreased T-Cell Receptor Excision Circles in Cutaneous T-Cell Lymphoma." Clinical Cancer Research 11, no. 16 (August 15, 2005): 5748–55. http://dx.doi.org/10.1158/1078-0432.ccr-04-2514.

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2

Fuleihan, Ramsay L. "DOCK8 deficiency, T cell receptor excision circles and newborn screening." Clinical Immunology 141, no. 2 (November 2011): 125–26. http://dx.doi.org/10.1016/j.clim.2011.08.002.

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3

Gul, Kiran A., Janne Strand, Rolf D. Pettersen, Henrik Brun, and Tore G. Abrahamsen. "T-cell Receptor Excision Circles in Newborns with Heart Defects." Pediatric Cardiology 41, no. 4 (March 13, 2020): 809–15. http://dx.doi.org/10.1007/s00246-020-02317-y.

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4

Somech, Raz. "T-cell receptor excision circles in primary immunodeficiencies and other T-cell immune disorders." Current Opinion in Allergy and Clinical Immunology 11, no. 6 (December 2011): 517–24. http://dx.doi.org/10.1097/aci.0b013e32834c233a.

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5

Miller, Jennifer M., and Lisa R. Forbes-Satter. "T-Cell Receptor Excision Circles in Newborns With Congenital Heart Disease." Pediatrics 146, Supplement 4 (December 2020): S376—S377. http://dx.doi.org/10.1542/peds.2020-023861kkkk.

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6

Ye, Ping, and Denise E. Kirschner. "Measuring Emigration of Human Thymocytes by T-Cell Receptor Excision Circles." Critical Reviews™ in Immunology 22, no. 5-6 (2002): 16. http://dx.doi.org/10.1615/critrevimmunol.v22.i5-6.80.

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7

Davey, Brooke T., Robert W. Elder, Michelle M. Cloutier, Nicholas Bennett, Ji Hyun Lee, Zhu Wang, Adrienne Manning, et al. "T-Cell Receptor Excision Circles in Newborns with Congenital Heart Disease." Journal of Pediatrics 213 (October 2019): 96–102. http://dx.doi.org/10.1016/j.jpeds.2019.05.061.

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8

Hsieh, Meng-Ying, Wan-Hsiang Hong, Jainn-Jim Lin, Wen-I. Lee, Kuang-Lin Lin, Huei-Shyong Wang, Shih-Hsiang Chen, Chao-Ping Yang, Tang-Her Jaing, and Jing-Long Huang. "T-cell receptor excision circles and repertoire diversity in children with profound T-cell immunodeficiency." Journal of Microbiology, Immunology and Infection 46, no. 5 (October 2013): 374–81. http://dx.doi.org/10.1016/j.jmii.2012.06.003.

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9

Lee, Wen-I., Jing-Long Huang, Syh-Jae Lin, Kuo-Wei Yeh, Li-Chen Chen, Liang-Shiou Ou, Tsung-Chieh Yao, et al. "Applying T-cell receptor excision circles and immunoglobulin κ-deleting recombination excision circles to patients with primary immunodeficiency diseases." Annals of Medicine 46, no. 7 (August 11, 2014): 555–65. http://dx.doi.org/10.3109/07853890.2014.941920.

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10

Hisazumi, Rinnosuke, Miya Kayumi, Ryuji Kikukawa, Tetsuo Nasu, and Masahiro Yasuda. "Detection and quantification of bovine signal joint T-cell receptor excision circles." Veterinary Immunology and Immunopathology 167, no. 1-2 (September 2015): 86–90. http://dx.doi.org/10.1016/j.vetimm.2015.06.010.

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11

Mauracher, Andrea A., Fabio Pagliarulo, Livia Faes, Stefano Vavassori, Tayfun Güngör, Lucas M. Bachmann, and Jana Pachlopnik Schmid. "Causes of low neonatal T-cell receptor excision circles: A systematic review." Journal of Allergy and Clinical Immunology: In Practice 5, no. 5 (September 2017): 1457–60. http://dx.doi.org/10.1016/j.jaip.2017.02.009.

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12

Du, Xin, Yangqiu Li, Shuxia Geng, Jianyu Weng, Zesheng Lu, and Rong Guo. "T Cell Receptor Excision Circles (TRECs) Decrease in Patients after Allogeneic Stem Cell Transplantation." Blood 106, no. 11 (November 16, 2005): 5357. http://dx.doi.org/10.1182/blood.v106.11.5357.5357.

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Abstract Human thymus is required for establishment of a T-cell pool in fetal life, T-cell emigration from thymus (thymic recent emigrants [TRECs]) is a continuous thymic-dependent process. To analyze the content of signal joint Tcell receptor excision DNA circles signal joint T cell receptor excision DNA circles(sjTRECs) within peripheral blood mononuclear cells (PBMCs), thereby to infer the level of naive T cells and the recent thymic output function in patients with allogeneic stem cell transplantation. We used real-time polymerase chain reaction (PCR) to quantify SjTRECs in 5 patients with chronic myeloid leukemia-chronic phase. Five patients(4 males, 1 females; median age 37 years,) who underwent HLA-matching sibling BMT and/or peripheral blood stem cell transplantation (PBSCT) at our department. Quantitative detection of sjTRECs in DNA of peripheral blood mononuclear cells from 13 normal individuals. The median value of sjTRECs copies P1 000 PBMCs was 4.37±3.64 in normal individuals whereas it was 0.57±0.51 copies P1 000 PBMCs in patients at least two years after allogeneic stem cell transplantation (P < 0. 03). We conclude that these Patients decrease in recent thymic output function,. Therefore, measurement of sjTREC may provide an important tool for predicting thymus-dependent T-cell reconstitution after transplantation.
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13

Profaizer, Tracie, and Patricia Slev. "A Multiplex, Droplet Digital PCR Assay for the Detection of T-Cell Receptor Excision Circles and Kappa-Deleting Recombination Excision Circles." Clinical Chemistry 66, no. 1 (December 30, 2019): 229–38. http://dx.doi.org/10.1373/clinchem.2019.308171.

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Abstract BACKGROUND T-cell receptor excision circles (TREC) and κ-deleting recombination receptor excision circles (KREC) concentrations can be used to assess and diagnose immune deficiencies, monitor thymic and bone marrow immune reconstitution, or follow responses to drug therapy. We developed an assay to quantify TREC, KREC, and a reference gene in a single reaction using droplet digital PCR (ddPCR). METHODS PCR was optimized for 3 targets: TREC, KREC, and ribonuclease P/MRP subunit p30 (RPP30) as the reference gene. Multiplexing was accomplished by varying the target's fluorophore and concentration. Correlation with clinical results was evaluated using 47 samples from healthy donors, 59 samples with T-cell and B-cell markers within the reference interval from the flow cytometry laboratory, 20 cord blood samples, and 34 samples submitted for exome sequencing for severe combined immunodeficiency disease (SCID). RESULTS The limit of the blank was 4 positive droplets, limit of detection 9 positive droplets, and limit of quantification 25 positive droplets, or 2.0 copies/μL. TREC and KREC copies/μL were as expected in the healthy donors and cord blood samples and concordant with the healthy flow cytometry results. Of the samples from the SCID Panel, 56.5% had a TREC count <20 copies/μL and 17.7% had a KREC count <20 copies/μL, suggestive of low T- and B-cell numbers, respectively. CONCLUSIONS Our multiplex ddPCR assay is an analytically sensitive and specific method for the absolute quantification of TREC and KREC. To the best of our knowledge, this paper is the first to describe the simultaneous quantification of TREC, KREC, and a reference gene by use of ddPCR.
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14

Salem, Lamyaa, Hala A. Talkhan, Salwa Bakr, Afaf A. Mostafa, and Nesrine A. Mohamed. "Simultaneous Quantification of T-Cell Receptor Excision Circles (TRECs) and K-Deleting Recombination Excision Circles (KRECs) by Real-time PCR." International Journal of Advanced Research 4, no. 4 (April 30, 2016): 1251–58. http://dx.doi.org/10.21474/ijar01/206.

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15

Profaizer, Tracie, Jeffrey Stevenson, Devin W. Close, and Patricia Slev. "P104 A real-time triplex pcr assay for quantifying T-cell receptor excision circles, kappa-deleting B-cell excision circles, and beta-actin." Human Immunology 79 (October 2018): 140. http://dx.doi.org/10.1016/j.humimm.2018.07.163.

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16

Punwani, Divya, Diana Gonzalez-Espinosa, Anne Marie Comeau, Amalia Dutra, Evgenia Pak, and Jennifer Puck. "Cellular calibrators to quantitate T-cell receptor excision circles (TRECs) in clinical samples." Molecular Genetics and Metabolism 107, no. 3 (November 2012): 586–91. http://dx.doi.org/10.1016/j.ymgme.2012.09.018.

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17

MORGUN, ANDREY, NATALIA SHULZHENKO, ADALBERTO SOCORRO-SILVA, ROSIANE V. Z. DINIZ, DIRCEU R. ALMEIDA, and MARIA GERBASE-DELIMA. "T Cell Receptor Excision Circles (TRECs) in Relation to Acute Cardiac Allograft Rejection." Journal of Clinical Immunology 24, no. 6 (November 2004): 612–16. http://dx.doi.org/10.1007/s10875-004-6246-1.

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18

Lan, Qing, Luoping Zhang, Fran Hakim, Min Shen, Sarfraz Memon, Guilan Li, Roel Vermeulen, et al. "Lymphocyte toxicity and T cell receptor excision circles in workers exposed to benzene." Chemico-Biological Interactions 153-154 (May 2005): 111–15. http://dx.doi.org/10.1016/j.cbi.2005.03.015.

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19

Chiarini, M., A. Sottini, D. Bertoli, F. Serana, L. Caimi, S. Rasia, R. Capra, and L. Imberti. "Newly produced T and B lymphocytes and T-cell receptor repertoire diversity are reduced in peripheral blood of fingolimod-treated multiple sclerosis patients." Multiple Sclerosis Journal 21, no. 6 (November 12, 2014): 726–34. http://dx.doi.org/10.1177/1352458514551456.

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Background: Fingolimod inhibits lymphocyte egress from lymphoid tissues, thus altering the composition of the peripheral lymphocyte pool of multiple sclerosis patients. Objective: The objective of this paper is to evaluate whether fingolimod determines a decrease of newly produced T- and B-lymphocytes in the blood and a reduction in the T-cell receptor repertoire diversity that may affect immune surveillance. Methods: Blood samples were obtained from multiple sclerosis patients before fingolimod therapy initiation and then after six and 12 months. Newly produced T and B lymphocytes were measured by quantifying T-cell receptor excision circles and K-deleting recombination excision circles by real-time PCR, while recent thymic emigrants, naive CD8+ lymphocytes, immature and naive B cells were determined by immune phenotyping. T-cell receptor repertoire was analyzed by complementarity determining region 3 spectratyping. Results: Newly produced T and B lymphocytes were significantly reduced in peripheral blood of fingolimod-treated patients. The decrease was particularly evident in the T-cell compartment. T-cell repertoire restrictions, already present before therapy, significantly increased after 12 months of treatment. Conclusions: These results do not have direct clinical implications but they may be useful for further understanding the mode of action of this immunotherapy for multiple sclerosis patients.
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20

Kuijpers, Taco W., Hanna IJspeert, Ester M. M. van Leeuwen, Machiel H. Jansen, Mette D. Hazenberg, Kees C. Weijer, Rene A. W. van Lier, and Mirjam van der Burg. "Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations." Blood 117, no. 22 (June 2, 2011): 5892–96. http://dx.doi.org/10.1182/blood-2011-01-329052.

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Abstract A girl presented during childhood with a single course of extensive chickenpox and moderate albeit recurrent pneumonia in the presence of idiopathic CD4+ T lymphocytopenia (ICL). Her clinical condition remained stable over the past 10 years without infections, any granulomatous disease, or autoimmunity. Immunophenotyping demonstrated strongly reduced naive T and B cells with intact proliferative capacity. Antibody reactivity on in vivo immunizations was normal. T-cell receptor-Vβ repertoire was polyclonal with a very low content of T-cell receptor excision circles (TRECs). Kappa-deleting recombination excision circles (KRECs) were also abnormal in the B cells. Both reflect extensive in vivo proliferation. Patient-derived CD34+ hematopoietic stem cells could not repopulate RAG2−/−IL2Rγc−/− mice, indicating the lymphoid origin of the defect. We identified 2 novel missense mutations in RAG1 (p.Arg474Cys and p.Leu506Phe) resulting in reduced RAG activity. This report gives the first genetic clue for ICL and extends the clinical spectrum of RAG mutations from severe immune defects to an almost normal condition.
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21

Cho, Sohee, Jianye Ge, Seung Bum Seo, Kiha Kim, Hye Young Lee, and Soong Deok Lee. "Age estimation via quantification of signal-joint T cell receptor excision circles in Koreans." Legal Medicine 16, no. 3 (May 2014): 135–38. http://dx.doi.org/10.1016/j.legalmed.2014.01.009.

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22

Cosper, A., and R. Eisenberg. "M242 EARLY DIAGNOSIS OF ATAXIA TELANGIECTASIA IDENTIFIED THROUGH LOW T-CELL RECEPTOR EXCISION CIRCLES." Annals of Allergy, Asthma & Immunology 125, no. 5 (November 2020): S82. http://dx.doi.org/10.1016/j.anai.2020.08.270.

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23

Patel, Jay P., Jennifer M. Puck, Rajgopal Srinivasan, Christina Brown, Uma Sunderam, Kunal Kundu, Steven E. Brenner, Richard A. Gatti, and Joseph A. Church. "Nijmegen Breakage Syndrome Detected by Newborn Screening for T Cell Receptor Excision Circles (TRECs)." Journal of Clinical Immunology 35, no. 2 (February 2015): 227–33. http://dx.doi.org/10.1007/s10875-015-0136-6.

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24

Patel, Jay, Jennifer M. Puck, Kunal Kundu, Uma Sunderam, Christina Brown, Rajgopal Srinivasan, Steven E. Brenner, Richard A. Gatti, and Joseph A. Church. "Nijmegen Breakage Syndrome Detected By Newborn Screening for T Cell Receptor Excision Circles (TRECs)." Journal of Allergy and Clinical Immunology 135, no. 2 (February 2015): AB14. http://dx.doi.org/10.1016/j.jaci.2014.12.979.

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25

Lutfeali, Shazia, David A. Khan, and Christian Wysocki. "A late preterm infant with lymphopenia." Allergy and Asthma Proceedings 41, no. 2 (March 1, 2020): 141–43. http://dx.doi.org/10.2500/aap.2019.40.190015.

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The newborn screen for severe combined immunodeficiency (SCID) uses real-time quantitative polymerase chain reaction for T-cell receptor excision circles and is highly sensitive for SCID. However, T-cell lymphopenia from other primary and secondary causes, such as DiGeorge syndrome, prematurity, thymic involution from stress, and thymectomy during cardiac surgery, is also detected. We present a newborn girl with T-cell lymphopenia of unknown etiology detected via abnormal newborn screen.
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26

Iwao, Noriaki, Junji Tanaka, Naoko Kato, Takeshi Kondo, Yoko Miura, Tomomi Toubai, Akio Shigematsu, et al. "Analysis of TREC (T Cell Receptor Excision Circles) Levels in CD94 Expressing CD8 T Cells in Chronic GVHD." Blood 106, no. 11 (November 16, 2005): 5367. http://dx.doi.org/10.1182/blood.v106.11.5367.5367.

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Abstract CD94 is one of the C-type lectin family members, forms a heterodimer with NKG2 gene family, and CD94 /NKG2A are inhibitory receptors. Not only NK cells but a subset of T cells express CD94/NKG2A, and previously we revealed the proportion of CD94/NKG2A expressing CD8 T cells were higher in patients with chronic graft versus host disease (GVHD), and CD94 expressing T cells have suppressive effects on mixed lymphocyte culture(MLC). We focus on CD94 positive T cell during T cell reconstitution after allogeneic hematopietic stem cell transplantation (allo-HSCT). T cell receptor excision circles (TREC) are suggested to be a useful marker of recent thymic output. In this study, we attempt to study TREC-containing CD8 T cell subset expressing CD94, and to examine the relation of TREC DNA level in CD94 expressing CD8 T cell and GVHD. We analyzed peripheral blood mononuclear cells (PBMCs) isolated from 24 patients (82 samples) undergone allo-HSCT including 15 patients with bone marrow transplantation and 9 patients with non-myeloablative stem cell transplantation. Informed consent was obtained from all patients. CD4 positive T cells were separated from PBMCs by magnetic cell sorting, and CD4 negative cell population was divided into CD94 positive CD8 T cells and CD94 negative CD8 T cells by fluorescence activated cell sorter. Genomic DNA was extracted from these separated T cell subsets. TREC DNA copy numbers per 105 isolated T cells (TREC level) were quantified by real time PCR. We investigated TREC levels in clinical status with pre-allo-HSCT, no episodes of GVHD or before manifestation of GVHD (No GVHD), chronic GVHD on disease (C-GVHD), and no symptoms and remission status of GVHD after immunosuppressive therapy (R-GVHD). Statical analyses were carried out by Mann-Whitney U test. There were no significant differences in TREC level of sorted CD4 positive T cells in C-GVHD compared with No GVHD (p=0.75) and R-GVHD (p=0.61), and also CD94 negative CD8 T cells in C-GVHD compared with No GVHD (p=0.79) and R-GVHD (p=0.20). On the other hand, TREC level of CD94 positive CD8 T cells in C-GVHD decreased in comparison with No GVHD (p=0.015) and R-GVHD (p=0.0019). The reduction of TREC level is thought to be induced not only by low thymic output but also by dilution of TREC concentration due to peripheral T cell expansion without duplications of TREC. These results may suggest that CD94 positive T cells play a role in modulation of GVHD, and proliferate during chronic GVHD with dilution of TREC in CD94 positive CD8 T cells. It is suggested that TREC level of CD94 expressing CD8 T cells may be useful markers of chronic GVHD.
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27

Devonshire, Ashley L., and Melanie Makhija. "Approach to primary immunodeficiency." Allergy and Asthma Proceedings 40, no. 6 (November 1, 2019): 465–69. http://dx.doi.org/10.2500/aap.2019.40.4273.

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Primary immunodeficiency diseases are inherited defects of the innate or adaptive arms of the immune system that lead to an increase in the incidence, frequency, or severity of infections and/or immune dysregulation. There may be defects in the adaptive arm of the immune system, including combined immunodeficiencies and antibody deficiency syndromes, or abnormalities in innate immunity, such as defects of phagocytes, the complement pathway, or toll-like receptor mediated signaling. Recurrent sinopulmonary infections with encapsulated bacteria such as Haemophilus influenzae type B or Streptococcus pneumoniae may be characteristic of an antibody deficiency syndrome. Frequent viral, fungal, or protozoal infections may suggest T lymphocyte impairment. Multiple Staphylococcus skin infections and fungal infections may imply neutrophil dysfunction or the Hyper-IgE syndrome, and recurrent Neisseria infection is a characteristic manifestation of late complement component (C5‐9, or the membrane attack complex) defects. Recurrent viral or pyogenic bacterial infections, often without the presence of a significant inflammatory response, suggest a defect in toll-like receptor signaling. Mycobacterial infections are characteristic of defects in the interleukin (IL) 12/interferon γ pathway. Screening of newborns for T-cell lymphopenia by using polymerase chain reaction to amplify T-cell receptor excision circles, which are formed when a T cell rearranges the variable region of its receptor, serves as a surrogate for newly synthesized naive T cells. Because of very low numbers of T-cell receptor excision circles, severe combined immunodeficiency, 22q11.2 syndrome, and other causes of T-cell lymphopenia have been identified in newborns.
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28

Li, B., Y. Q. Li, L. J. Yang, S. H. Chen, W. Yu, J. Y. Chen, and W. W. Liu. "Decreased T-cell receptor excision DNA circles in peripheral blood mononuclear cells among benzene-exposed workers." International Journal of Immunogenetics 36, no. 2 (April 2009): 107–11. http://dx.doi.org/10.1111/j.1744-313x.2009.00832.x.

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29

Knutsen, Alan P., Mei W. Baker, and M. Louise Markert. "Interpreting low T-cell receptor excision circles in newborns with DiGeorge anomaly: Importance of assessing naive T-cell markers." Journal of Allergy and Clinical Immunology 128, no. 6 (December 2011): 1375–76. http://dx.doi.org/10.1016/j.jaci.2011.08.019.

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30

Valotti, Monica, Alessandra Sottini, Arnalda Lanfranchi, Federica Bolda, Federico Serana, Diego Bertoli, Viviana Giustini, Marion Vaglio Tessitore, Luigi Caimi, and Luisa Imberti. "Long-Lasting Production of New T and B Cells and T-Cell Repertoire Diversity in Patients with Primary Immunodeficiency Who Had Undergone Stem Cell Transplantation: A Single-Centre Experience." Journal of Immunology Research 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/240453.

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Levels of Kappa-deleting recombination excision circles (KRECs), T-cell receptor excision circles (TRECs), and T-cell repertoire diversity were evaluated in 1038 samples of 124 children with primary immunodeficiency, of whom 102 (54 with severe combined immunodeficiency and 48 with other types of immunodeficiency) underwent hematopoietic stem cell transplantation. Twenty-two not transplanted patients with primary immunodeficiency were used as controls. Only data of patients from whom at least five samples were sent to the clinical laboratory for routine monitoring of lymphocyte reconstitutions were included in the analysis. The mean time of the follow-up was 8 years. The long-lasting posttransplantation kinetics of KREC and TREC production occurred similarly in patients with severe combined immunodeficiency and with other types of immunodeficiency and, in both groups, the T-cell reconstitution was more efficient than in nontransplanted children. Although thymic output decreased in older transplanted patients, the degree of T-cell repertoire diversity, after an initial increase, remained stable during the observation period. However, the presence of graft-versus-host disease and ablative conditioning seemed to play a role in the time-related shaping of T-cell repertoire. Overall, our data suggest that long-term B- and T-cell reconstitution was equally achieved in children with severe combined immunodeficiency and with other types of primary immunodeficiency.
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31

Hazenberg, Mette D., Sigrid A. Otto, Elmar S. de Pauw, Helene Roelofs, Willem E. Fibbe, Dörte Hamann, and Frank Miedema. "T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events." Blood 99, no. 9 (May 1, 2002): 3449–53. http://dx.doi.org/10.1182/blood.v99.9.3449.

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Abstract It is generally believed that homeostatic responses regulate T-cell recovery after peripheral stem cell transplantation (PSCT). We studied in detail immune recovery in relation to T-cell depletion and clinical events in a group of adult patients who underwent PSCT because of hematologic malignancies. Initially, significantly increased proportions of dividing naive, memory, and effector CD4+and CD8+ T cells were found that readily declined, despite still very low numbers of CD4+ and CD8+ T cells. After PSCT, increased T-cell division rates reflected immune activation because they were associated with episodes of infectious disease and graft-versus-host disease (GVHD). T-cell receptor excision circles (TRECs) were measured to monitor thymic output of naive T cells. Mean TREC content normalized rapidly after PSCT, long before naive T-cell numbers had significantly recovered. This is compatible with the continuous thymic production of TREC+ naive T cells and does not reflect homeostatic increases of thymic output. TREC content was decreased in patients with GVHD and infectious complications, which may be explained by the dilution of TRECs resulting from increased proliferation. Combining TREC and Ki67 analysis with repopulation kinetics led to the novel insight that recovery of TREC content and increased T-cell division during immune reconstitution after transplantation are related to clinical events rather than to homeostatic adaptation to T-cell depletion.
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32

Hisazumi, Rinnosuke, Miya Kayumi, Weidong Zhang, Ryuji Kikukawa, Tetuo Nasu, and Masahiro Yasuda. "Evaluation of bovine thymic function by measurement of signal joint T-cell receptor excision circles." Veterinary Immunology and Immunopathology 169 (January 2016): 74–78. http://dx.doi.org/10.1016/j.vetimm.2015.12.009.

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33

Ye, Ping, and Denise E. Kirschner. "Reevaluation of T Cell Receptor Excision Circles as a Measure of Human Recent Thymic Emigrants." Journal of Immunology 168, no. 10 (May 15, 2002): 4968–79. http://dx.doi.org/10.4049/jimmunol.168.10.4968.

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34

Cho, Sohee, Hee Jin Seo, Ji Hyun Lee, Moon Young Kim, and Soong Deok Lee. "Influence of immunologic status on age prediction using signal joint T cell receptor excision circles." International Journal of Legal Medicine 131, no. 4 (February 1, 2017): 1061–67. http://dx.doi.org/10.1007/s00414-017-1540-7.

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35

Wagner, John L., Irina Kakhniashvili, Bijoyesh Mookerjee, Joanne Filicko, Dolores Grosso, and Neal Flomenberg. "Assessment of T-Cell Reconstitution After Two Step Haploidentical Stem Cell Transplants by Measurement of T-Cell Receptor Excision Circles (TREC)." Biology of Blood and Marrow Transplantation 19, no. 2 (February 2013): S210. http://dx.doi.org/10.1016/j.bbmt.2012.11.237.

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36

Barycheva, L. Yu, L. S. Khachirova, L. T. L.T.Kubanova, O. V. Kalyuzhin, and M. V. Golubeva. "Detection of T-cell receptor excision circles and κ-deleting recombination excision circles in the diagnosis of primary immunodeficiency: retrospective analysis of clinical cases." Voprosy praktičeskoj pediatrii 14, no. 6 (2019): 98–103. http://dx.doi.org/10.20953/1817-7646-2019-6-98-103.

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37

Göngrich, Christina, Olov Ekwall, Mikael Sundin, Nicholas Brodszki, Anders Fasth, Per Marits, Sam Dysting, et al. "First Year of TREC-Based National SCID Screening in Sweden." International Journal of Neonatal Screening 7, no. 3 (August 25, 2021): 59. http://dx.doi.org/10.3390/ijns7030059.

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Screening for severe combined immunodeficiency (SCID) was introduced into the Swedish newborn screening program in August 2019 and here we report the results of the first year. T cell receptor excision circles (TRECs), kappa-deleting element excision circles (KRECs), and actin beta (ACTB) levels were quantitated by multiplex qPCR from dried blood spots (DBS) of 115,786 newborns and children up to two years of age, as an approximation of the number of recently formed T and B cells and sample quality, respectively. Based on low TREC levels, 73 children were referred for clinical assessment which led to the diagnosis of T cell lymphopenia in 21 children. Of these, three were diagnosed with SCID. The screening performance for SCID as the outcome was sensitivity 100%, specificity 99.94%, positive predictive value (PPV) 4.11%, and negative predictive value (NPV) 100%. For the outcome T cell lymphopenia, PPV was 28.77%, and specificity was 99.95%. Based on the first year of screening, the incidence of SCID in the Swedish population was estimated to be 1:38,500 newborns.
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38

Prince, Benjamin T., and John M. Routes. "Abnormal T-Cell Receptor Excision Circle Newborn Screen: What Next?" Journal of Allergy and Clinical Immunology: In Practice 6, no. 1 (January 2018): 318–19. http://dx.doi.org/10.1016/j.jaip.2017.07.047.

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39

Pahwa, Savita, Vivek Chitnis, Richard M. Mitchell, Sanjit Fernandez, Alamelu Chandrasekharan, Craig M. Wilson, and Steven D. Douglas. "CD4+and CD8+T Cell Receptor Repertoire Perturbations with Normal Levels of T Cell Receptor Excision Circles in HIV-Infected, Therapy-Naive Adolescents." AIDS Research and Human Retroviruses 19, no. 6 (June 2003): 487–95. http://dx.doi.org/10.1089/088922203766774531.

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40

Chiarini, Marco, Cinzia Zanotti, Federico Serana, Alessandra Sottini, Diego Bertoli, Luigi Caimi, and Luisa Imberti. "T-cell receptor and K-deleting recombination excision circles in newborn screening of T- and B-cell defects: review of the literature and future challenges." Journal of Public Health Research 2, no. 1 (May 1, 2013): 3. http://dx.doi.org/10.4081/jphr.2013.e3.

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Since its introduction as a public health programme in the United States in the early 1960s, newborn blood screening (NBS) has evolved from the detection of phenylalanine levels on filter paper to the application of DNA-based technologies to identify T-cell lymphopenia in infants with severe combined immunodeficiency. This latter use of NBS has required the development of an assay for T-cell lymphopenia based on the quantification of T-cell receptor excision circles (TRECs) that could be performed on dried blood spots routinely collected from newborn infants. The TREC-based NBS was developed six years ago, and there have already been 7 successful pilot studies since then. Similarly, efforts are now being made to establish a screen for B-cell defects, in particular agammaglobulinaemia, taking advantage of the introduction of the method for the quantification of K-deleting recombination excision circles (KRECs). A further achievement of NBS could be the simultaneous recognition of T- and B-cell defects using the combined quantification of TRECs and KRECs from Guthrie card blood spots. This approach may help the early identification of infants with T- and B-cell deficiencies so that they can then be referred to specialised paediatric centres, where a precise diagnosis of severe combined immunodeficiency and agammaglobulinaemia can be performed, and where then they can immediately receive specific therapy. Simultaneous TREC and KREC quantification should also allow classification of patients into subgroups and help identify children with less serious primary immunodeficiencies. This would help avoid the opportunistic infections and frequent hospitalisations that result from a late or lack of diagnosis.
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41

Du, Xin, Yangqiu Li, Jianyu Weng, Zesheng Lu, Rong Guo, Shaohua Chen, Lijian Yang, Suxia Geng, and Zhilun Huang. "Analysis T Cell Receptor Excision Circles (TRECs) in Patients with Graft-Versus-Host Disease (GVHD) after Allogeneic Stem Cell Transplantation." Blood 108, no. 11 (November 16, 2006): 5272. http://dx.doi.org/10.1182/blood.v108.11.5272.5272.

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Abstract The thymic-dependent pathway that involves generation of new naive T cells from donor-derived precursor cells accounts for the more durable reconstitution of the T-cell compartment and generates a more diverse TCR repertoire. Thymic function and production of recent thymic emigrants (RTEs) may be directly evaluated through the quantification, by real-time polymerase chain reaction (PCR), of the T-cell receptor excision circles (TRECs). Following hematopoietic stem cell transplant (HSCT), there is a prolonged period of profound immune deficiency, which continues for years after HSCT. The factors that inhibit thymic function may include age, graft-versus-host disease (GVHD), and direct thymic damage from chemoradiotherapy. GVHD after HSCT also leads to thymic insufficiency, possibly by direct attack on the thymic stroma by allogeneic effector cells. The aim of our study is to analysis T cell receptor excision circles (TRECs) in patients with GVHD after allogeneic stem cell transplantation. We used real-time polymerase chain reaction (PCR) to quantify SjTRECs in 12 patients with GVHD(9 males, 3 females; median age 32 years old), who underwent HLA-matching sibling BMT and/or peripheral blood stem cell transplantation (PBSCT) at our department. Quantitative detection of sjTRECs in DNA of peripheral blood mononuclear cells from 13 normal individualals. The median value of sjTRECs copies P1 000 PBMCs was 4.37±3.64 in normal indiviuals. However, the decreased levels of TRECs were most profound in the group of patients with active chronic GVHD at the time of study. it was 0.26±0.22 copies P1 000 PBMCs in 12 patients with GVHD (P < 0. 00007). We conclude that measurement of sjTREC may provide an important tool for predicting thymus-dependent T-cell reconstitution in GVHD patients after transplantation.
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42

Broers, Annoek E. C., Jules P. P. Meijerink, Jacques J. M. van Dongen, Sandra J. Posthumus, Bob Löwenberg, Eric Braakman, and Jan J. Cornelissen. "Quantification of newly developed T cells in mice by real-time quantitative PCR of T-cell receptor rearrangement excision circles." Experimental Hematology 30, no. 7 (July 2002): 745–50. http://dx.doi.org/10.1016/s0301-472x(02)00825-1.

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43

Quiros-Roldan, E., B. Zanini, A. Ferraresi, M. Castellano, V. Giustini, A. Sottini, F. Castelli, and L. Imberti. "Peripheral loss of regulatory T cells and polyautoimmunity in an HIV-infected patient." International Journal of STD & AIDS 29, no. 13 (July 27, 2018): 1345–47. http://dx.doi.org/10.1177/0956462418785997.

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We report a case of a human immunodeficiency virus (HIV)/hepatitis C virus-co-infected patient with an optimal virological status but with a poor CD4+ cell profile, followed up in the University Department of Infectious and Tropical Diseases of Brescia, Italy. He presented several autoimmune diseases (ADs) over the years concomitant with CD4+ cell increase episodes following severe immune depression of unknown cause. We studied T- and B-cell subsets and found low levels of K-deleting Recombination Excision Circles, T-cell Receptor Excision Circles and B and T memory subpopulations, which indicated that the bone marrow and thymic outputs were lower than in healthy controls. The most relevant phenotypic alteration was in the regulatory T-cell (Treg) population, because total Tregs as well as naïve, central memory and effector memory cells were detected at very low levels. This was the first case of polyautoimmunity defined as the presence of more than one AD in the same individual, occurring in an HIV patient. Several factors may be implicated, including genetic susceptibility, environmental factors, concomitant therapies and dysregulation of immune system cells. The extremely low number of Tregs found in our patient may play a major role in the regulation of the immune response and the development of all ADs.
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De Vera, Michelle J., Lena Al-Harthi, and Anita T. Gewurz. "Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision circles." Annals of Allergy, Asthma & Immunology 93, no. 5 (November 2004): 478–84. http://dx.doi.org/10.1016/s1081-1206(10)61416-0.

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45

Morinishi, Yoichi, Kohsuke Imai, Noriko Nakagawa, Hiroki Sato, Katsuyuki Horiuchi, Yoshitoshi Ohtsuka, Yumi Kaneda, et al. "Identification of Severe Combined Immunodeficiency by T-Cell Receptor Excision Circles Quantification Using Neonatal Guthrie Cards." Journal of Pediatrics 155, no. 6 (December 2009): 829–33. http://dx.doi.org/10.1016/j.jpeds.2009.05.026.

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46

Strawa, Katarzyna, Anna Markowska, Piotr Miśkiewicz, Aleksander Kuś, Urszula Ambroziak, Konrad Szymański, Renata Zbiec, et al. "Increased concentration of T-cell receptor rearrangement excision circles (TREC) in peripheral blood in Graves' disease." Clinical Endocrinology 81, no. 5 (June 12, 2014): 769–74. http://dx.doi.org/10.1111/cen.12492.

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47

Ravkov, Eugene, Patricia Slev, and Nahla Heikal. "Thymic output: Assessment of CD4+ recent thymic emigrants and T-Cell receptor excision circles in infants." Cytometry Part B: Clinical Cytometry 92, no. 4 (January 28, 2016): 249–57. http://dx.doi.org/10.1002/cyto.b.21341.

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48

Richardson, Max W., Andrij E. Sverstiuk, Peter Silvera, Jack Greenhouse, Julianna Lisziewicz, Franco Lori, Kamel Khalili, Mark G. Lewis, and Jay Rappaport. "T-Cell Receptor Excision Circles (TREC) in SHIV 89.6p and SIVmac251 Models of HIV-1 Infection." DNA and Cell Biology 23, no. 1 (January 2004): 1–13. http://dx.doi.org/10.1089/104454904322745880.

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49

Kamae, Chikako, Noriko Nakagawa, Hiroki Sato, Kenichi Honma, Noriko Mitsuiki, Osamu Ohara, Hirokazu Kanegane, et al. "Common variable immunodeficiency classification by quantifying T-cell receptor and immunoglobulin κ-deleting recombination excision circles." Journal of Allergy and Clinical Immunology 131, no. 5 (May 2013): 1437–40. http://dx.doi.org/10.1016/j.jaci.2012.10.059.

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50

Samstein, M., Y. Hamzavi Abedi, Z. Treyster, and A. Jongco. "COMPLEMENT DEFICIENCY IN TWO PATIENTS WITH ABSENCE OF T-CELL RECEPTOR EXCISION CIRCLES ON NEWBORN SCREENING." Annals of Allergy, Asthma & Immunology 121, no. 5 (November 2018): S96—S97. http://dx.doi.org/10.1016/j.anai.2018.09.316.

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