Allaoui Abire, Moundir Abderrahmane, Benhsaien Ibtihal, Ailal Fatima, Bakkouri Jalila El, Echchilali Khadija, Naitlho Abdelhamid, Kabli Hassan El, Bousfiha Ahmed Aziz, Moudatir Mina
Clinical Immunology, Inflammation and Allergy Laboratory (LICIA), Faculty of Medicine and Pharmacy, University of Hassan II Casablanca, Casablanca, Morocco.
Immunopathology-Immunotherapy-Immunomonitoring Laboratory, Faculty of Medicine, Mohammed VI University of Health and Sciences, Casablanca, Morocco.
Front Immunol. 2025 Jul 9;16:1602820. doi: 10.3389/fimmu.2025.1602820. eCollection 2025.
Common Variable Immunodeficiency (CVID) is the most prevalent symptomatic inborn errors of immunity (IEI), characterized by impaired antibody production, recurrent infections, and immune dysregulation. While extensively studied in Western populations, data from North Africa remains scarce. This study provides the first comprehensive evaluation of the clinical, immunological, and genetic landscape of CVID in a Moroccan nationwide cohort.
A multicenter, cross-sectional study was conducted across eight university hospitals in Morocco from 2019 to 2025. Sixty-one CVID patients were enrolled according to ESID (European society of immunodeficiency) and MENA (Middle-East and North Africa) guidelines. Clinical, immunological, and genetic data were analyzed. Whole-blood samples were processed for immunophenotyping, and a subset of patients underwent next-generation sequencing (NGS) targeting 474 inborn error of immunity (IEI)-associated genes.
The mean age at diagnosis was 25.9 (SD 18.7) years old, with a diagnostic delay of 6.91 (SD 8.82) years. The most frequent infectious complications were pulmonary infections (88.5%) and gastrointestinal infections (63.9%). Non-infectious complications were present in 49.2% of patients, with predominant features including lymphoproliferation (50.8%), autoimmune cytopenias (39.3%), and granulomatous disease (18%). Bronchiectasis was the most common pulmonary finding (44.3%). Genetic testing (n=25) revealed 19 pathogenic variants in 13 genes, including 14 novel variants, particularly , and . The phenotype-genotype correlation, based on clinical presentation, gene function, and multidisciplinary assessment, was strong in 52.6% of cases.
This study provides Morocco's first clinical and genetic landscape of CVID, highlighting a high prevalence of consanguinity-associated monogenic defects and a significant burden of infectious and immune dysregulatory complications. Our findings emphasize the need for early diagnosis, multidisciplinary management, and access to targeted therapies in non-Western settings. Further studies with functional validation of genetic variants are warranted to refine precision medicine approaches in CVID.
常见变异型免疫缺陷（CVID）是最常见的有症状的先天性免疫缺陷（IEI），其特征为抗体产生受损、反复感染和免疫失调。虽然在西方人群中已进行了广泛研究，但来自北非的数据仍然稀少。本研究首次对摩洛哥全国队列中CVID的临床、免疫和遗传情况进行了全面评估。
2019年至2025年在摩洛哥的八所大学医院开展了一项多中心横断面研究。根据欧洲免疫缺陷学会（ESID）和中东及北非（MENA）指南纳入了61例CVID患者。对临床、免疫和遗传数据进行了分析。对全血样本进行免疫表型分析，部分患者接受了针对474个与先天性免疫缺陷（IEI）相关基因的二代测序（NGS）。
诊断时的平均年龄为25.9（标准差18.7）岁，诊断延迟为6.91（标准差8.82）年。最常见的感染并发症是肺部感染（88.5%）和胃肠道感染（63.9%）。49.2%的患者存在非感染性并发症，主要特征包括淋巴细胞增殖（50.8%）、自身免疫性血细胞减少（39.3%）和肉芽肿病（18%）。支气管扩张是最常见的肺部表现（44.3%）。基因检测（n = 25）在13个基因中发现了19个致病变异，包括14个新变异，特别是 、 和 。基于临床表现、基因功能和多学科评估的表型-基因型相关性在52.6%的病例中很强。
本研究提供了摩洛哥CVID的首个临床和遗传情况，突出了近亲结婚相关单基因缺陷的高患病率以及感染和免疫失调并发症的重大负担。我们的研究结果强调了在非西方环境中进行早期诊断、多学科管理和获得靶向治疗的必要性。有必要开展进一步的基因变异功能验证研究，以完善CVID中的精准医学方法。
