Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
Int Arch Allergy Immunol. 2020;181(9):706-714. doi: 10.1159/000508817. Epub 2020 Jul 2.
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.
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.
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.
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.
普通变异性免疫缺陷（CVID）是最常见的原发性免疫缺陷疾病，主要表现为反复细菌感染，此外还存在其他免疫缺陷，包括 B 细胞缺失或功能障碍以及免疫球蛋白水平降低。在本研究中，我们的目的是评估具有原发性临床 CVID 诊断和自身免疫表型并具有明确遗传诊断的患者的临床、免疫和分子数据。
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，有 83 名患者进行了基因检查，选择了 27 名具有自身免疫性和明确遗传突变的患者进行分析。对研究人群进行了全外显子组测序和确认性 Sanger 测序方法。回顾性地为所有患者填写了一份问卷，以评估人口统计学、实验室、临床和遗传数据。
在 27 名研究患者中，确定了 11 种不同的遗传缺陷，最常见的突变基因是 LRBA，报告了 17 名（63.0%）患者。两名患者（7.7%）表现出自身免疫性并发症，作为免疫缺陷的首发表现。11 名患者（40.7%）发生了一种自身免疫，16 名患者（59.3%）进展为多自身免疫。大多数单自身免疫患者（n = 9，90.0%）主要发生感染性并发症，而在多自身免疫患者中，最常见的首发表现是肠病（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。最常见的自身免疫表现为血液学（40.7%）、胃肠道（48.1%）、风湿病（25.9%）和皮肤病学（22.2%）疾病。多自身免疫患者的调节性 T 细胞低于单自身免疫患者。
在我们的队列中，大多数患者的自身免疫性疾病的诊断先于原发性免疫缺陷的诊断。这种关联突出了这样一个事实，即有自身免疫表现的患者应接受体液免疫评估。
