The HLA-B –21 M/T dimorphism associates with disease severity in COVID-19
Genes & Immunity, 2024
Strunz B., Momayyezi P., Bilev E., Muvva J., Chen P., Bister J., Schaffer M., Akber M., Cornillet M., Aleman S., Berglin L., Bergsten H., Brighenti S., Brownlie D., Buggert M., Butrym M., Chambers B., Cuapio A., Lozano I., Dillner L., Djärv T., Dzidic M., Emgård J., Eriksson L., Flodström-Tullberg M., Glans H., Gorin J., Grip J., Haroun-Izquierdo A., Henriksson E., Hertwig L., Kalsum S., Kammann T., Klingström J., Kokkinou E., Kvedaraite E., Loreti M., Lourda M., Maleki K., Malmberg K., Marquardt N., Mårtensson J., Maucourant C., Michaëlsson J., Mjösberg J., Moll K., Nauclér P., Norrby-Teglund A., Palma Medina L., Parrot T., Perez-Potti A., Persson B., Radler L., Religa D., Ringqvist E., Rivera-Ballesteros O., Rooyackers O., Sandberg J., Sandberg J., Sekine T., Sohlberg E., Soini T., Sönnerborg A., Strålin K., Svensson M., Tynell J., Unge C., Varnaite R., von Kries A., Wullimann D., Horowitz A., Malmberg K., Rooyackers O., Aleman S., Ljunggren H., Björkström N., Strålin K., Hammer Q.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Serum | O Olink Target 96 |
Abstract
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.