Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children’s Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.
Int Arch Allergy Immunol

中文翻译：

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与常见可变免疫缺陷和自身免疫性相关的单基因原发性免疫缺陷疾病。

背景：普通可变免疫缺陷病（CVID）是最常见的原发性免疫缺陷病，主要特征是细菌反复感染以及其他免疫缺陷，包括B细胞丧失或功能障碍以及免疫球蛋白水平降低。在这项研究中，我们的目的是评估具有CVID和自身免疫表型的主要临床诊断并经遗传学诊断的患者的临床，免疫学和分子数据。方法：在伊朗儿童医学中心医院的伊朗原发性免疫缺陷登记处登记的297名CVID患者中，对83名患者进行了基因检查，对27名具有自身免疫性和确诊基因突变的患者进行了分析。全外显子组测序和验证性Sanger测序方法用于研究人群。回顾性填写了所有患者的问卷，以评估人口统计学，实验室，临床和遗传数据。结果：在27名研究患者中，鉴定出11种不同的遗传缺陷，最常见的突变基因是LRBA。，在17名（63.0％）患者中报告。两名患者（7.7％）显示出自身免疫性并发症为免疫缺陷的首例表现。11例患者（40.7％）发生了一种自身免疫，16例患者（59.3％）进行了多自身免疫。大多数具有单自身免疫性的患者（n = 9，90.0％）主要发生感染并发症，而具有多自身免疫性的患者，最常见的首发症状是肠病（n= 6，37.6％）。在13名患者（61.9％）中，自身免疫性疾病的诊断先于原发性免疫缺陷的诊断。自身免疫最常见的表现是血液系统疾病（40.7％），胃肠道疾病（48.1％），风湿病（25.9％）和皮肤病（22.2％）。多自体免疫患者的调节性T细胞低于单自体免疫患者。结论：在我们的队列中，在大多数患者中，自身免疫性疾病的诊断先于原发性免疫缺陷的诊断。这种联系突出了这样一个事实，即应该对转诊有自身免疫表现的患者进行体液免疫评估。
Int Arch过敏免疫