Variable Abnormalities in T and B Cell Subsets in Ataxia Telangiectasia
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ORIGINAL ARTICLE
Variable Abnormalities in T and B Cell Subsets in Ataxia Telangiectasia Tannaz Moeini Shad 1,2 & Bahman Yousefi 1 & Parisa Amirifar 2,3 & Samaneh Delavari 2 & William Rae 4,5 & Parviz Kokhaei 6,7 & Hassan Abolhassani 2,8,9 & Asghar Aghamohammadi 2 & Reza Yazdani 2 Received: 21 July 2020 / Accepted: 29 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background Ataxia-telangiectasia (AT) is a rare genetic condition, caused by biallelic deleterious variants in the ATM gene, and has variable immunological abnormalities. This study aimed to examine immunologic parameters reflecting cell development, activation, proliferation, and class switch recombination (CSR) and determine their relationship to the clinical phenotype in AT patients. Methods In this study, 40 patients with a confirmed diagnosis of AT from the Iranian immunodeficiency registry center and 28 age-sex matched healthy controls were enrolled. We compared peripheral B and T cell subsets and T cell proliferation response to CD3/CD28 stimulation in AT patients with and without CSR defects using flow cytometry. Results A significant decrease in naïve, transitional, switched memory, and IgM only memory B cells, along with a sharp increase in the marginal zone-like and CD21low B cells was observed in the patients. We also found CD4+ and CD8+ naïve, central memory, and terminally differentiated effector memory CD4+ (TEMRA) T cells were decreased. CD4+ and CD8+ effector memory, CD8+ TEMRA, and CD4+ regulatory T cells were significantly elevated in our patients. CD4+ T cell proliferation was markedly impaired compared to the healthy controls. Moreover, immunological investigations of 15 AT patients with CSR defect revealed a significant reduction in the marginal zone, switched memory, and more intense defects in IgM only memory B cells, CD4+ naïve and central memory T cells. Conclusion The present study revealed that patients with AT have a broad spectrum of cellular and humoral deficiencies. Therefore, a detailed evaluation of T and B cell subsets increases understanding of the disease in patients and the risk of infection. Keywords Primary immunodeficiency . ataxia telangiectasia . B cell subsets . T cell subsets . class switch recombination (CSR) . flow cytometry . proliferation assay Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00881-9) contains supplementary material, which is available to authorized users. * Asghar Aghamohammadi [email protected] * Reza Yazdani [email protected] 1
Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
2
Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
3
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
4
Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambri
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