ABSTRACT

Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement caused by homozygous or compound heterozygous mutations in the ataxia telangiectasia mutated (ATM) gene which encodes a serine/threonine protein kinase. The aims of this study were to investigate class switch recombination (CSR) and to review the clinical and immunologic phenotypes of 3 groups of A-T patients, including A-T patients with CSR defects (CSR-D), A-T patients with selective immunoglobulin A deficiency (IgA-D) and A-T patients with normal Ig level.

Methods: In this study, 41 patients with confirmed diagnosis of A-T (16 A-T patients with HIgM, 15 A-T patients with IgA-D, and 10 A-T patients with normal Ig levels) from Iranian immunodeficiency registry center were enrolled. B-cell proliferation, in vitro CSR toward IgE and IgA were compared between three groups as well as G2 radiosensitivity assay.

Results: Earliest presentation of telangiectasia was a significant hallmark in A-T patients with CSR-D (p = .036). In this investigation, we found that the frequency of respiratory infection (p = .002), pneumonia (p = .02), otitis media (p = .008), chronic fever (p < .001), autoimmunity (p = .02) and hepatosplenomegaly (p = .03) in A-T patients with HIgM phenotype were significantly higher than the other groups. As expected IgE production stimulation and IgA CSR were perturbed in HIgM patients that were aligned with the higher readiosenstivity scores in this group.

Conclusion: A-T patients with HIgM compared to other A-T patients presenting more infections and noninfectious complications, therefore, early detection and careful management of these patients is necessary.

摘要

目的：共济失调毛细血管扩张症 (AT) 是一种常染色体隐性神经退行性疾病，由编码丝氨酸/苏氨酸蛋白激酶的共济失调毛细血管扩张症 (ATM)基因纯合或复合杂合突变引起的多系统受累。本研究的目的是调查类别转换重组 (CSR) 并回顾 3 组 AT 患者的临床和免疫表型，包括具有 CSR 缺陷 (CSR-D) 的 AT 患者、具有选择性免疫球蛋白 A 缺陷 (IgA) 的 AT 患者-D) 和 Ig 水平正常的 AT 患者。

方法：在这项研究中，来自伊朗免疫缺陷登记中心的 41 名确诊为 AT 的患者（16 名 HIgM 的 AT 患者，15 名 IgA-D 的 AT 患者和 10 名 Ig 水平正常的 AT 患者）入选。比较三组之间的B 细胞增殖、对 IgE 和 IgA 的体外CSR 以及 G2 放射敏感性测定。

结果：毛细血管扩张的最早表现是 CSR-D 的 AT 患者的一个重要标志 ( p = .036)。在本次调查中，我们发现呼吸道感染 ( p = .002)、肺炎 ( p = .02)、中耳炎 ( p = .008)、慢性发热 ( p < .001)、自身免疫 ( p = .001)的频率。 02) 和肝脾肿大 ( p = .03) 在具有 HIgM 表型的 AT 患者中显着高于其他组。正如预期的那样，HIgM 患者的 IgE 产生刺激和 IgA CSR 受到干扰，这与该组中较高的易敏性评分一致。

结论：与其他 AT 患者相比，具有 HIgM 的 AT 患者具有更多的感染和非感染性并发症，因此，对这些患者进行早期发现和仔细管理是必要的。