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 Science, Tehran, Iran.
Pediatr Allergy Immunol. 2021 Aug;32(6):1335-1348. doi: 10.1111/pai.13510. Epub 2021 May 13.
The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations.
We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data.
A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity.
Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.
先天性免疫缺陷（IEI）是一组异质性疾病，主要表现为严重且反复发生的感染，此外还包括自身免疫和炎症性疾病等并发症。本研究旨在评估有和无自身免疫表现的单基因 IEI 患者的临床、免疫和分子数据。
我们回顾性筛选了伊朗 PID 登记处的单基因 IEI 病例，以观察自身免疫和免疫失调的发生情况。为所有符合条件的单基因缺陷患者填写了一份问卷，以评估人口统计学、实验室、临床和分子数据。
本研究共纳入 461 例单基因 IEI 患者（男 290 例，女 171 例），中位（IQR）年龄为 11.0（6.0-20.0）岁。总体而言，331 例（72.1%）患者的父母为近亲。研究时，330 例（75.7%）患者存活，106 例（24.3%）死亡。92 例（20.0%）患者出现自身免疫，自身免疫诊断的中位（IQR）年龄为 4.0（2.0-7.0）岁。16 例（3.5%）患者表现出自免疫并发症（主要为自身免疫性血细胞减少症），为疾病的首发表现。大多数自身免疫患者临床诊断为普通变异型免疫缺陷（42.4%）。自身免疫患者的鼻窦和脾肿大发生率明显高于无自身免疫患者。在自身免疫患者中，最常见的致病性变异发生在 LRBA（21 例，23.0%）、ATM（13 例，14.0%）和 BTK（9 例，10.0%）基因中。在不同基因的自身免疫评估中，4 例 IL10RB（100%）、3 例 AIRE（100%）和 30 例 LRBA（70.0%）突变基因的自身免疫患病率最高。
自身免疫现象是单基因 IEI 患者的常见特征，并与疾病更复杂的病程相关。因此，当遇到自身免疫性疾病时，特别是在免疫球蛋白血症异常的情况下，早期发现负责免疫失调的相关基因进行下一代测序是合适的。
