Clinical and immunological spectrum of MHC class I deficiency: insights from a long-term cohort with two novel mutations.

IF 5.9 2区医学 Q1 IMMUNOLOGY

Frontiers in Immunology Pub Date : 2025-10-07 eCollection Date: 2025-01-01 DOI:10.3389/fimmu.2025.1675097

Sule Haskologlu, Aydan Ikinciogullari, Candan Islamoglu, Sevgi Kostel Bal, Deniz Bayrakoglu, Serife Erdem, Zeynep Ceren Karahan, Omur Ardeniz, Caner Aytekin, Aylin Heper, Serdar Ceylaner, Figen Dogu

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Abstract

Background: Major histocompatibility complex (MHC) Class I deficiency is a rare form of primary immunodeficiency that typically presents with recurrent sinopulmonary infections, bronchiectasis, and granulomatous skin lesions during late childhood or adolescence.

Methods: This retrospective study describes the clinical, immunological, and long-term follow-up data of 11 patients diagnosed MHC Class I deficiency.

Results: The cohort included 11 patients (6 males, 5 females) with a median age of 26 years (range 19-44). The median age at diagnosis was 19 years, with a diagnostic delay of 14 years. Bronchiectasis was seen in 10 patients, granulomatous skin lesions in 6, uveitis in 5, and nasal septum perforation in 3. All but one patient survived during a median follow-up of 11 years. HLA-ABC expression ranged from 0% to 73%, with persistently low mean fluorescence intensity (0.4-3.8). IgM levels were reduced in 7 patients. Ten patients were persistently positive for anti-rubella IgM, including all six with granulomatous skin lesions. Immunophenotyping revealed reduced CD3⁺ (n=2), CD4⁺ (n=3), CD8⁺ (n=3), CD19⁺ (n=5), CD3^-CD16⁺CD56⁺ (n=3), CD19+ IgM-27+ IgD- (switched memory B cells) (n=7), and CD19+ IgM-27+ IgD+ (marginal zone B cells) (n=8). All patients had elevated γδ+ T cells, and NK cells were reduced in three. Seven patients had TAP1 and four had TAP2 mutations, with no significant genotype-phenotype differences.

Conclusion: MHC Class I deficiency presents a broad clinical spectrum from asymptomatic to life-threatening disease. Granulomatous tissue damage and uveitis contributed to morbidity. Persistent rubella-specific IgM in most patients, including those without granulomas, is a novel serologic finding that may reflect altered antiviral immunity. Its clinical significance remains uncertain and, further studies with tissue-based viral detection are needed to clarify this observation.

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MHC I类缺陷的临床和免疫学谱：来自两个新突变的长期队列的见解。

背景：主要组织相容性复合体（MHC） I类缺乏是一种罕见的原发性免疫缺陷，通常表现为儿童晚期或青春期复发性肺感染、支气管扩张和肉芽肿性皮肤病变。方法：本回顾性研究描述了11例诊断为MHC I类缺乏的患者的临床、免疫学和长期随访资料。结果：该队列包括11例患者（6男5女），中位年龄26岁（范围19-44岁）。诊断时的中位年龄为19岁，诊断延迟14年。支气管扩张10例，肉芽肿性皮肤病变6例，葡萄膜炎5例，鼻中隔穿孔3例。在平均11年的随访期间，除1名患者外，其余患者均存活。HLA-ABC的表达范围为0% ~ 73%，平均荧光强度持续较低（0.4 ~ 3.8）。7例患者IgM水平降低。10例患者抗风疹IgM持续阳性，包括所有6例肉芽肿性皮肤病变。免疫表型分析显示CD3+ (n=2)、CD4+ (n=3)、CD8+ (n=3)、CD19+ (n=5)、CD3- cd16 +CD56+ (n=3)、CD19+ IgM-27+ IgD-（开关记忆B细胞）（n=7）和CD19+ IgM-27+ IgD+（边缘区B细胞）（n=8）减少。所有患者γδ+ T细胞均升高，3例患者NK细胞减少。7例患者有TAP1突变，4例患者有TAP2突变，基因型-表型无显著差异。结论：MHC I类缺乏表现出从无症状到危及生命的广泛临床谱。肉芽肿性组织损伤和葡萄膜炎导致发病。在大多数患者中，包括那些没有肉芽肿的患者，持续的风疹特异性IgM是一种新的血清学发现，可能反映了抗病毒免疫的改变。其临床意义尚不确定，需要进一步的组织病毒检测研究来澄清这一观察结果。

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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来源期刊

Frontiers in Immunology IMMUNOLOGY-

CiteScore

9.80

自引率

11.00%

发文量

7153

审稿时长

14 weeks

期刊介绍： Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.