Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
J Clin Immunol. 2023 May;43(4):819-834. doi: 10.1007/s10875-023-01442-6. Epub 2023 Feb 15.
Primary B cell defects manifesting as predominantly antibody deficiencies result from variable inborn errors of the B cell lineage and their development, including impairments in early bone marrow development, class switch recombination (CSR), or terminal B cell differentiation. In this study, we aimed to investigate autoimmunity in monogenic patients with B cell development and differentiation defects.
Patients with known genetic defects in the B cell development and differentiation were recruited from the Iranian inborn errors of immunity registry.
A total of 393 patients with a known genetic defect in the B cell development and differentiation (257 males; 65.4%) with a median age of 12 (6-20) years were enrolled in this study. After categorizing patients, 109 patients had intrinsic B cell defects. More than half of the patients had defects in one of the ATM (85 patients), BTK (76 patients), LRBA (34 patients), and DOCK8 (33 patients) genes. Fifteen patients (3.8%) showed autoimmune complications as their first manifestation. During the course of the disease, autoimmunity was reported in 81 (20.6%) patients at a median age of 4 (2-7) years, among which 65 patients had mixed intrinsic and extrinsic and 16 had intrinsic B cell defects. The comparison between patients with the mentioned four main gene defects showed that the patient group with LRBA defect had a significantly higher frequency of autoimmunity compared to those with other gene defects. Based on the B cell defect stage, 13% of patients with early B cell defect, 17% of patients with CSR defect, and 40% of patients who had terminal B cell defect presented at least one type of autoimmunity.
Our results demonstrated that gene mutations involved in human B cell terminal stage development mainly LRBA gene defect have the highest association with autoimmunity.
主要表现为抗体缺陷的原发性 B 细胞缺陷是由 B 细胞谱系及其发育的各种先天性错误引起的，包括早期骨髓发育、类别转换重组（CSR）或终末 B 细胞分化受损。在这项研究中，我们旨在研究具有 B 细胞发育和分化缺陷的单基因患者的自身免疫。
从伊朗先天性免疫缺陷登记处招募具有 B 细胞发育和分化已知遗传缺陷的患者。
本研究共纳入 393 名 B 细胞发育和分化存在已知遗传缺陷的患者（257 名男性；65.4%），中位年龄为 12（6-20）岁。在对患者进行分类后，有 109 名患者存在内在 B 细胞缺陷。超过一半的患者存在 ATM（85 名患者）、BTK（76 名患者）、LRBA（34 名患者）和 DOCK8（33 名患者）基因之一的缺陷。15 名患者（3.8%）以自身免疫并发症为首发表现。在疾病过程中，81 名（20.6%）患者在中位年龄为 4（2-7）岁时出现自身免疫，其中 65 名患者存在混合内在和外在缺陷，16 名患者存在内在 B 细胞缺陷。对上述四个主要基因缺陷的患者进行比较，结果显示 LRBA 缺陷患者组的自身免疫发生率明显高于其他基因缺陷患者组。根据 B 细胞缺陷阶段，早期 B 细胞缺陷的患者中有 13%、CSR 缺陷的患者中有 17%、终末 B 细胞缺陷的患者中有 40%至少出现一种自身免疫。
我们的研究结果表明，涉及人类 B 细胞终末阶段发育的基因突变主要与 LRBA 基因缺陷相关，与自身免疫的关联度最高。
