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Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19

PURPOSE: Host genetic variants may contribute to severity of COVID-19. NKG2C(+) NK cells are potent antiviral effector cells, potentially limiting the extent of SARS-CoV-2 infections. NKG2C is an activating NK cell receptor encoded by the KLRC2 gene, which binds to HLA-E on infected cells leading to...

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Detalles Bibliográficos
Autores principales: Vietzen, Hannes, Zoufaly, Alexander, Traugott, Marianna, Aberle, Judith, Aberle, Stephan W., Puchhammer-Stöckl, Elisabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: , The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835668/
https://www.ncbi.nlm.nih.gov/pubmed/33500568
http://dx.doi.org/10.1038/s41436-020-01077-7
Descripción
Sumario:PURPOSE: Host genetic variants may contribute to severity of COVID-19. NKG2C(+) NK cells are potent antiviral effector cells, potentially limiting the extent of SARS-CoV-2 infections. NKG2C is an activating NK cell receptor encoded by the KLRC2 gene, which binds to HLA-E on infected cells leading to NK cell activation. Heterozygous or homozygous KLRC2 deletion (KLRC2(del)) may naturally occur and is associated with a significantly lower or absent NKG2C expression level. In addition, HLA-E*0101/0103 genetic variants occur, caused by a single-nucleotide polymorphism. We therefore investigated whether the severity of COVID-19 is associated with these genetic variants. METHODS: We investigated the distribution of KLRC2 deletion and HLA-E*0101/0103 allelic variants in a study cohort of 361 patients with either mild (N = 92) or severe (N = 269) COVID-19. RESULTS: Especially the KLRC2(del), and at a lower degree the HLA-E*0101, allele were significantly overrepresented in hospitalized patients (p = 0.0006 and p = 0.01), particularly in patients requiring intensive care (p < 0.0001 and p = 0.01), compared with patients with mild symptoms. Both genetic variants were independent risk factors for severe COVID-19. CONCLUSION: Our data show that these genetic variants in the NKG2C/HLA-E axis have a significant impact on the development of severe SARS-CoV-2 infections, and may help to identify patients at high-risk for severe COVID-19.