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Variable Abnormalities in T and B Cell Subsets in Ataxia Telangiectasia Publisher Pubmed



Moeini Shad T1, 2 ; Yousefi B1 ; Amirifar P2, 3 ; Delavari S2 ; Rae W4, 5 ; Kokhaei P6, 7 ; Abolhassani H2, 8, 9 ; Aghamohammadi A2 ; Yazdani R2
Authors
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Authors Affiliations
  1. 1. Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
  2. 2. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom
  5. 5. Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom
  6. 6. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
  7. 7. Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden
  8. 8. Research Center for Primary Immunodeficiencies, Iran University of Medical Sciences, Tehran, Iran
  9. 9. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden

Source: Journal of Clinical Immunology Published:2021


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 naive, 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+ naive, 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+ naive 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. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
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