Variable Abnormalities in T and B Cell Subsets in Ataxia Telangiectasia

• Published in: Journal of clinical immunology Vol. 41; no. 1; pp. 76 - 88
• Main Authors: Moeini Shad, Tannaz, Yousefi, Bahman, Amirifar, Parisa, Delavari, Samaneh, Rae, William, Kokhaei, Parviz, Abolhassani, Hassan, Aghamohammadi, Asghar, Yazdani, Reza
• Format: Journal Article
• Language: English
• Published: New York Springer US 2021; Springer Nature B.V
• Subjects: Adolescent; Ataxia; Ataxia telangiectasia; Ataxia Telangiectasia - diagnosis; Ataxia Telangiectasia - etiology; Ataxia telangiectasia mutated protein; Ataxia Telangiectasia Mutated Proteins - genetics; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; Biomarkers; Biomedical and Life Sciences; Biomedicine; CD28 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Cell activation; Cell growth; Cell proliferation; Child; Class switching; Comorbidity; Female; Flow cytometry; Genetic Predisposition to Disease; Genetic Variation; Humans; Immunodeficiency; Immunoglobulin M; Immunologic Memory; Immunological memory; Immunology; Immunophenotyping; Immunoregulation; Infectious Diseases; Internal Medicine; Lymphocyte Activation; Lymphocyte Count; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Medical Microbiology; Medicin och hälsovetenskap; Memory cells; Original Article; Phenotype; Phenotypes; Recombination; Severity of Illness Index; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; proliferation assay; ataxia telangiectasia; class switch recombination (CSR); flow cytometry; B cell subsets; T cell subsets; Primary immunodeficiency
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-020-00881-9

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 CD21
low
B cells was observed in the patients. We also found CD4
+
and CD8
+
naïve, 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
+
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.