Activating Killer-Cell Immunoglobulin-Like Receptors Are Associated With the Severity of Coronavirus Disease 2019.
J Infect Dis
; 224(2): 229-240, 2021 07 15.
Article
in English
| MEDLINE | ID: covidwho-1310926
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 (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 versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, Pâ <â 7.7â ×â 10-9). In patients with mild and/or moderate infection, HLA-B*1501 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%; Pâ <â .002; Pcâ =â 0.022). This strongly suggests that HLA-B*1501 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Genetic Predisposition to Disease
/
Receptors, KIR
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
J Infect Dis
Year:
2021
Document Type:
Article
Affiliation country:
Infdis
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