Publication: Activating Killer-cell Immunoglobulin-like Receptors are associated with the severity of COVID-19
Authors
Bernal, Enrique ; Alcaraz, María J. ; Quadee, Ahmed A. ; Moreno, Marta ; Martínez-Sánchez, María V. ; Campillo, José A. ; Gómez, Jose M. ; Peláez, Ana ; García-Vázquez, Elisa ; Herranz, Maite ; Hernández-Olivo, Marta ; Martínez-Alfaro, Elisa ; Alcaraz, Antonia ; Muñoz, Ángeles ; Cano, Alfredo ; McKay, Matthew R. ; Muro, Manuel ; Minguela, Alfredo ; Murcian COVID19 Study group ; Gimeno Arias, Lourdes
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Publisher
Oxford University Press
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DOI
https://doi.org/10.1093/infdis/jiab228
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info:eu-repo/semantics/article
Description
©2021 The Author(s). . This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. This document is the Accepted, version of a Published Work that appeared in final form in The Journal of Infectious Diseases. To access the final edited and published work see https://doi.org/10.1093/infdis/jiab228
Abstract
Background: Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. Here we investigate the role of Killer-cell Immunoglobulin-like receptor (KIR)/Human Leukocyte Antigen Class-I (HLA-I) interactions in the susceptibility and severity of COVID-19. Methods: KIR and HLA-I genotyping and NK cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 non-infected controls. Results: NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe than mild/moderate patients and controls (83.7%, 55.7% and 36.2%, p<7.7x10-9). In mild/moderate patients HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared to patients with other HLA-B*15 subtypes and non-infected controls (90.9%, 42.9% and 47.3%, p<0.002, Pc=0.022). This strongly suggests that HLA-B*15:01 specifically presenting SARS-CoV-2 peptides could form a neo-ligand interacting with KIR3DS1. Similarly, a putative neo-ligand for KIR2DS4 could arise from other HLA-I molecules presenting SARS-CoV-2 peptides expressed on infected/activated lung antigen presenting cells. Conclusions: Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/Ligand interactions associated to disease severity.
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Citation
The Journal of Infectious Diseases. 2021, 224(2):229-240
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/