Defects in Innate and Intrinsic Immunity in Morocco: A Retrospective Analysis of the Genetic Landscape and Clinical Correlations.

Q1 Medicine

Pathogens and Immunity Pub Date : 2025-11-03 eCollection Date: 2025-01-01 DOI:10.20411/pai.v10i2.845

Marwa Refaat, Chaymae Oujane, Abderrahmane Errami, Zahra Aadam, Abderrahmane Moundir, Bouchra Baghad, Sanae Zaidi, Halima Kholaiq, Assiya El Kettani, Ibtihal Benhsaien, Fatima Ailal, Asmaa Drissi Bourhanbour, Jalila El Bakkouri, Ahmed Aziz Bousfiha

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Abstract

Background: Susceptibility to common infectious diseases is often linked to innate immune deficiencies. Patients may present normal standard immunological profiles but remain highly vulnerable to infections, complicating diagnosis. This study investigates innate and intrinsic immune deficiencies and their genetic underpinnings in Moroccan patients, emphasizing early detection and personalized care.

Methods: A retrospective analysis was conducted using data from the Moroccan Inborn Errors of Immunity (IEI) registry (2008-2024). Included were patients with confirmed innate or intrinsic immunodeficiencies based on CBC, CRP, immunoglobulin levels, lymphocyte subpopulations, and whole-exome sequencing. Classification followed the 2022 IUIS criteria.

Results: Among 884 patients with IEI, 79 (∼9%) had innate or intrinsic immunodeficiencies, with genetic confirmation in 46 (58%). Of these, 23 (50%) were diagnosed with Mendelian susceptibility to mycobacterial disease (MSMD), involving mutations in the IL12RB1, STAT1, IFNGR1, SPPL2A, TYK2, and TBX21 (T-bet) genes. Chronic mucocutaneous candidiasis (CMC) was found in 15 (32%) patients, linked to STAT1 and IL17RA mutations. Severe viral infection predisposition was seen in 3 patients (POLR3A, IFIH1, TLR7XL) and bacterial susceptibility in 3 others (IRF4, IFNGR1, NCSTN). Novel variants were identified, including IRAK4 c.277delT (p.F93fsX26), not previously reported, and SNORA31 (n.36T>C), previously seen in Saudi Arabia, now found in a Moroccan case of herpes simplex encephalitis.

Conclusion: This study reveals the genetic complexity of innate immune disorders in Morocco, with a notable prevalence of MSMD and CMC. It underscores the value of early genetic screening to guide diagnosis and improve patient outcomes.

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摩洛哥先天和内在免疫缺陷：遗传景观和临床相关性的回顾性分析。

背景：对常见传染病的易感性通常与先天免疫缺陷有关。患者可能表现出正常的标准免疫特征，但仍然极易受到感染，使诊断复杂化。本研究调查了摩洛哥患者的先天和内在免疫缺陷及其遗传基础，强调早期发现和个性化护理。方法：采用2008-2024年摩洛哥先天性免疫错误（IEI）登记数据进行回顾性分析。包括根据CBC、CRP、免疫球蛋白水平、淋巴细胞亚群和全外显子组测序证实先天性或内在免疫缺陷的患者。分类遵循2022年IUIS标准。结果：在884例IEI患者中，79例（约9%）有先天或内在免疫缺陷，46例（58%）有遗传证实。其中，23例（50%）被诊断为分枝杆菌病孟德尔易感性（MSMD），涉及IL12RB1、STAT1、IFNGR1、SPPL2A、TYK2和TBX21 （T-bet）基因突变。15例（32%）患者发现慢性粘膜皮肤念珠菌病（CMC），与STAT1和IL17RA突变有关。3例患者（POLR3A、IFIH1、TLR7XL）有严重病毒感染易感，另外3例患者（IRF4、IFNGR1、NCSTN）有细菌易感。发现了新的变异，包括以前未报道的irak4c . 277delt (p.F93fsX26)，以及以前在沙特阿拉伯发现的SNORA31 (n.36T bbbbc)，现在在摩洛哥的一例单纯疱疹脑炎病例中发现。结论：本研究揭示了摩洛哥先天免疫疾病的遗传复杂性，其中MSMD和CMC的患病率显著。它强调了早期遗传筛查在指导诊断和改善患者预后方面的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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