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.

中文翻译：

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共济失调毛细血管扩张症中 T 和 B 细胞亚群的可变异常

背景

共济失调毛细血管扩张症 (AT) 是一种罕见的遗传病，由ATM基因中的双等位有害变异引起，并且具有可变的免疫异​​常。本研究旨在检查反映细胞发育、活化、增殖和类别转换重组 (CSR) 的免疫学参数，并确定它们与 AT 患者临床表型的关系。

方法

在这项研究中，来自伊朗免疫缺陷登记中心的 40 名确诊为 AT 的患者和 28 名年龄性别匹配的健康对照者入组。我们使用流式细胞术比较了有和没有 CSR 缺陷的 AT 患者的外周 B 和 T 细胞亚群以及 T 细胞对 CD3/CD28 刺激的增殖反应。

结果

在患者中观察到幼稚、过渡记忆、转换记忆和仅 IgM 记忆 B 细胞显着减少，同时边缘区样和 CD21^低B 细胞急剧增加。我们还发现 CD4 ⁺和 CD8 ⁺幼稚、中央记忆和终末分化效应记忆 CD4 ⁺ (T _EMRA ) T 细胞减少。在我们的患者中，CD4 ⁺和 CD8 ⁺效应记忆、CD8 ⁺ T _EMRA和 CD4 ⁺调节性 T 细胞显着升高。 CD4 ⁺与健康对照相比，T 细胞增殖明显受损。此外，对 15 名患有 CSR 缺陷的 AT 患者的免疫学研究显示，边缘区显着减少、转换记忆，以及仅 IgM 记忆 B 细胞、CD4 ⁺幼稚和中央记忆 T 细胞的更严重缺陷。

结论

本研究表明，AT 患者存在广泛的细胞和体液缺陷。因此，对 T 和 B 细胞亚群的详细评估可以增加对患者疾病和感染风险的了解。