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-21 M/T 二态性及其在 COVID-19 中的潜在作用研究。

Investigation of -21 M/T Dimorphism and Its Potential Role in COVID-19.

作者信息

Martín-Rodríguez David, Gutiérrez-Bautista Juan Francisco, Bernal Mónica, Rodriguez-Nicolas Antonio, Vílchez José Ramón, Marín-Sánchez Ana, Rosales-Castillo Antonio, Sainz Juan, Cabrera-Serrano Antonio José, Ceron-Hernandez Jorge, López-Nevot Miguel Ángel, Ruiz-Cabello Francisco, Jiménez Pilar

机构信息

Servicio de Análisis Clínicos e Inmunología, University Hospital Virgen de las Nieves, 18014 Granada, Spain.

Departamento de Bioquímica, Biología Molecular e Inmunología III, University of Granada, 18016 Granada, Spain.

出版信息

Int J Mol Sci. 2025 Jul 3;26(13):6419. doi: 10.3390/ijms26136419.

DOI:10.3390/ijms26136419
PMID:40650195
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12250186/
Abstract

Natural killer (NK) cells play a key role in the innate immune response against viral infections. Their activity is regulated by a balance of activating and inhibitory signals, which are modulated by interactions with HLA class I molecules, including HLA-E. The 21M/T dimorphism influences the availability of HLA-B leader peptides that stabilize HLA-E expression and modulate NK cell function via the NKG2A/CD94 receptor. To investigate the association between the -21M/T dimorphism and the clinical severity of COVID-19, we analyzed a cohort of hospitalized patients with primary SARS-CoV-2 infection, who were genotyped for the -21M/T dimorphism. Clinical data, lymphocyte counts, the neutrophil-to-lymphocyte ratio (NLR), and inflammatory markers were compared across genotypes. Contrary to previous studies suggesting a protective effect of the M/M genotype, we found no significant association between the -21M/T dimorphism and COVID-19 severity, lymphocyte parameters, or inflammatory biomarkers. Our findings do not support a role for the -21M/T dimorphism in modulating COVID-19 outcomes. These results underscore the complexity of NK cell regulation and highlight the need for integrative studies combining genetic, immunological, and functional data to better understand host factors influencing disease progression.

摘要

自然杀伤（NK）细胞在针对病毒感染的先天免疫反应中起关键作用。它们的活性由激活信号和抑制信号的平衡调节，这些信号通过与包括HLA-E在内的HLA I类分子相互作用而被调节。-21M/T二态性影响稳定HLA-E表达并通过NKG2A/CD94受体调节NK细胞功能的HLA-B前导肽的可用性。为了研究-21M/T二态性与COVID-19临床严重程度之间的关联，我们分析了一组原发性SARS-CoV-2感染的住院患者队列，对其进行了-21M/T二态性基因分型。比较了不同基因型的临床数据、淋巴细胞计数、中性粒细胞与淋巴细胞比率（NLR）和炎症标志物。与先前研究表明M/M基因型具有保护作用相反，我们发现-21M/T二态性与COVID-19严重程度、淋巴细胞参数或炎症生物标志物之间无显著关联。我们的研究结果不支持-21M/T二态性在调节COVID-19结局中的作用。这些结果强调了NK细胞调节的复杂性，并突出了结合遗传、免疫和功能数据进行综合研究以更好地理解影响疾病进展的宿主因素的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6899/12250186/e41796ac1b1d/ijms-26-06419-g005.jpg
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本文引用的文献

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