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Activating Killer-cell Immunoglobulin-like Receptors are associated with the severity of COVID-19

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dc.contributor.authorBernal, Enrique
dc.contributor.authorAlcaraz, María J.
dc.contributor.authorQuadee, Ahmed A.
dc.contributor.authorMoreno, Marta
dc.contributor.authorMartínez-Sánchez, María V.
dc.contributor.authorCampillo, José A.
dc.contributor.authorGómez, Jose M.
dc.contributor.authorPeláez, Ana
dc.contributor.authorGarcía-Vázquez, Elisa
dc.contributor.authorHerranz, Maite
dc.contributor.authorHernández-Olivo, Marta
dc.contributor.authorMartínez-Alfaro, Elisa
dc.contributor.authorAlcaraz, Antonia
dc.contributor.authorMuñoz, Ángeles
dc.contributor.authorCano, Alfredo
dc.contributor.authorMcKay, Matthew R.
dc.contributor.authorMuro, Manuel
dc.contributor.authorMinguela, Alfredo
dc.contributor.authorMurcian COVID19 Study group
dc.contributor.authorGimeno Arias, Lourdes
dc.contributor.departmentMedicina
dc.date.accessioned2024-07-02T11:29:23Z
dc.date.available2024-07-02T11:29:23Z
dc.date.issued2021-04-30
dc.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/jiab228es
dc.description.abstractBackground: 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.es
dc.formatapplication/pdfes
dc.format.extent35es
dc.identifier.citationThe Journal of Infectious Diseases. 2021, 224(2):229-240
dc.identifier.doihttps://doi.org/10.1093/infdis/jiab228
dc.identifier.issnPrint: 0022-1899
dc.identifier.issnElectronic: 1537-6613
dc.identifier.urihttp://hdl.handle.net/10201/142807
dc.languageenges
dc.publisherOxford University Presses
dc.relationThis work was funded by MINECO - Instituto de Salud Carlos III (COV20/00377); Co-funded by European Regional Development Fund (ERDF), “A way to make Europe”; M.J. Alcaraz was funded by Murcian Association for the Investigation and Study of Infection Diseases (AMIEI). M.V. Martínez-Sánchez was funded by the Asociación Pablo Ugarte (APU).es
dc.relation.publisherversionhttps://academic.oup.com/jid/article/224/2/229/6259338es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectSARS-CoV-2es
dc.subjectCOVID-19 severityes
dc.subjectNK cellses
dc.subjectActivating KIR receptorses
dc.subjectHLA class-Ies
dc.titleActivating Killer-cell Immunoglobulin-like Receptors are associated with the severity of COVID-19es
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublicationa0170301-b64f-46f8-810a-ff18c9bf0a5f
relation.isAuthorOfPublication.latestForDiscoverya0170301-b64f-46f8-810a-ff18c9bf0a5f
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