tetano
Editor, Senior Moderator
J Infect Dis
. 2021 Apr 30;jiab228.
doi: 10.1093/infdis/jiab228. Online ahead of print.
Activating Killer-cell Immunoglobulin-like Receptors are associated with the severity of COVID-19
Enrique Bernal[SUP] 1 [/SUP], Lourdes Gimeno[SUP] 2 3 [/SUP], Mar?a J Alcaraz[SUP] 1 [/SUP], Ahmed A Quadeer[SUP] 4 [/SUP], Marta Moreno[SUP] 5 [/SUP], Mar?a V Mart?nez-S?nchez[SUP] 2 [/SUP], Jos? A Campillo[SUP] 2 [/SUP], Jose M Gomez[SUP] 5 [/SUP], Ana Pelaez[SUP] 6 [/SUP], Elisa Garc?a[SUP] 7 [/SUP], Maite Herranz[SUP] 5 [/SUP], Marta Hern?ndez-Olivo[SUP] 8 [/SUP], Elisa Mart?nez-Alfaro[SUP] 9 [/SUP], Antonia Alcaraz[SUP] 1 [/SUP], ?ngeles Mu?oz[SUP] 1 [/SUP], Alfredo Cano[SUP] 1 [/SUP], Matthew R McKay[SUP] 4 10 [/SUP], Manuel Muro[SUP] 2 [/SUP], Alfredo Minguela[SUP] 2 [/SUP]
Affiliations
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 (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 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.
Keywords: COVID-19 severity; HLA class-I; NK cells; SARS-Cov-2; activating KIR receptors.
. 2021 Apr 30;jiab228.
doi: 10.1093/infdis/jiab228. Online ahead of print.
Activating Killer-cell Immunoglobulin-like Receptors are associated with the severity of COVID-19
Enrique Bernal[SUP] 1 [/SUP], Lourdes Gimeno[SUP] 2 3 [/SUP], Mar?a J Alcaraz[SUP] 1 [/SUP], Ahmed A Quadeer[SUP] 4 [/SUP], Marta Moreno[SUP] 5 [/SUP], Mar?a V Mart?nez-S?nchez[SUP] 2 [/SUP], Jos? A Campillo[SUP] 2 [/SUP], Jose M Gomez[SUP] 5 [/SUP], Ana Pelaez[SUP] 6 [/SUP], Elisa Garc?a[SUP] 7 [/SUP], Maite Herranz[SUP] 5 [/SUP], Marta Hern?ndez-Olivo[SUP] 8 [/SUP], Elisa Mart?nez-Alfaro[SUP] 9 [/SUP], Antonia Alcaraz[SUP] 1 [/SUP], ?ngeles Mu?oz[SUP] 1 [/SUP], Alfredo Cano[SUP] 1 [/SUP], Matthew R McKay[SUP] 4 10 [/SUP], Manuel Muro[SUP] 2 [/SUP], Alfredo Minguela[SUP] 2 [/SUP]
Affiliations
- PMID: 33928374
- DOI: 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 (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 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.
Keywords: COVID-19 severity; HLA class-I; NK cells; SARS-Cov-2; activating KIR receptors.