Strunz Benedikt, Momayyezi Pouria, Bilev Eleni, Muvva Jagadeeswara Rao, Chen Puran, Bister Jonna, Schaffer Marie, Akber Mira, Cornillet Martin, Horowitz Amir, Malmberg Karl-Johan, Rooyackers Olav, Aleman Soo, Ljunggren Hans-Gustaf, Björkström Niklas K, Strålin Kristoffer, Hammer Quirin
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Genes Immun. 2025 Feb;26(1):70-74. doi: 10.1038/s41435-024-00302-6. Epub 2024 Nov 1.
Host genetics shape immune responses and influence severity of infectious diseases. The HLA-B -21 M/T dimorphism tunes the functionality of natural killer (NK) cells expressing the inhibitory receptor NKG2A. NKG2A NK cells have been reported to recognize SARS-CoV-2-infected cells, but it remains unclear whether the HLA-B -21 M/T dimorphism associates with COVID-19 severity. Here, we investigated the influence of the HLA-B -21 M/T dimorphism in a cohort of 230 unvaccinated patients hospitalized with COVID-19 and requiring respiratory support. We found that HLA-B -21 M/M genotypes were more prevalent in patients with moderate compared to severe COVID-19 (6.0% vs. 0.9%). Comparison of age- and sex-matched sub-groups revealed that patients with M/M genotypes required mechanical respiratory support less frequently (OR = 0.13, 95% CI = 0.01-0.76, P = 0.013). Furthermore, patients with M/M genotypes showed a coordinately shifted signature of clinical laboratory parameters, coinciding with elevated serum levels of the anti-viral cytokine IFN-γ. These findings demonstrate that HLA-B variants associate with COVID-19 severity and suggest that the robust functionality of NKG2A NK cells in patients carrying the M/M genotype may contribute to protection from severe disease.
宿主基因塑造免疫反应并影响传染病的严重程度。HLA - B -21 M/T二态性调节表达抑制性受体NKG2A的自然杀伤（NK）细胞的功能。据报道，NKG2A NK细胞可识别感染SARS-CoV-2的细胞，但HLA - B -21 M/T二态性是否与COVID-19的严重程度相关仍不清楚。在此，我们调查了HLA - B -21 M/T二态性对230名因COVID-19住院且需要呼吸支持的未接种疫苗患者队列的影响。我们发现，与重症COVID-19患者相比，中度患者中HLA - B -21 M/M基因型更为普遍（6.0%对0.9%）。年龄和性别匹配亚组的比较显示，M/M基因型患者需要机械呼吸支持的频率较低（OR = 0.13，95% CI = 0.01 - 0.76，P = 0.013）。此外，M/M基因型患者的临床实验室参数特征出现协同变化，同时血清抗病毒细胞因子IFN-γ水平升高。这些发现表明，HLA - B变异与COVID-19的严重程度相关，并表明携带M/M基因型患者中NKG2A NK细胞的强大功能可能有助于预防重症疾病。
