Activating Killer-Cell Immunoglobulin-Like Receptors Are Associated With the Severity of Coronavirus Disease 2019. (30th April 2021)

• Record Type: Journal Article
• Authors: Bernal, Enrique; Gimeno, Lourdes; Alcaraz, María J; Quadeer, Ahmed A; Moreno, Marta; Martínez-Sánchez, María V; Campillo, José A; Gomez, Jose M; Pelaez, Ana; García, Elisa; Herranz, Maite; Hernández-Olivo, Marta; Martínez-Alfaro, Elisa; Alcaraz, Antonia; Muñoz, Ángeles; Cano, Alfredo; McKay, Matthew R; Muro, Manuel; Minguela, Alfredo
• Is Part Of: Journal of infectious diseases. Volume 224:Number 2(2021)
• Page Start: 229
• Page End: 240
• Publication Date: 2021-04-30
• Subjects: activating KIR receptors -- COVID-19 severity -- HLA class-I -- NK cells -- SARS-Cov-2; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab228
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. In this study, 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: We performed KIR and HLA-I genotyping and natural killer cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 noninfected controls. Results: The NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4 low CD16 low CD226 low CD56 high TIGIT high NKG2A high ), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P < 7.7 × 10 −9 ). In patients with mild and/or moderate infection, HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared with patients with other HLA-B*15 subtypes and noninfected controls (90.9%, 42.9%, and 47.3%; P < .002; Pc = 0.022). This strongly suggests that HLA-B*15:01 specifically presenting severe acute respiratory syndrome coronavirus 2 peptides could form a neoligand interacting with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 could arise from other HLA-I molecules presenting severe acute respiratory syndrome coronavirus 2 peptides expressed on infected an/or 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 with disease severity.