Variable Abnormalities in T and B Cell Subsets in Ataxia Telangiectasia

Background Ataxia-telangiectasia (AT) is a rare genetic condition, caused by biallelic deleterious variants in theATMgene, 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 CD21(low)B cells was observed in the patients. We also found CD4(+)and CD8(+)naive, central memory, and terminally differentiated effector memory CD4(+)(T-EMRA) T cells were decreased. CD4(+)and CD8(+)effector memory, CD8(+)T(EMRA), 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.

Automated summary

Patients with AT exhibit a wide range of cellular and humoral deficiencies, including significant alterations in B and T cell subsets, as well as impaired cell proliferation capabilities. CSR defects further exacerbate these abnormalities.