HLA-E*01:01 + HLA-E*01:01 genotype confers less susceptibility to COVID-19, while HLA-E*01:03 + HLA-E*01:03 genotype is associated with more severe disease |
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Affiliation: | 1. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran;2. Iran University of Medical Science, Tehran, Iran |
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Abstract: | BackgroundHLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8+ T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have different levels of expression and affinity for MHC Ia-derived peptide raises the question of whether HLA-E polymorphisms affect susceptibility to COVID-19 or its severity.Methods104 COVID-19 convalescent plasma donors with/without history of hospitalization and 18 blood donors with asymptomatic COVID-19, all were positive for anti-SARS-CoV-2 IgG antibody as well as a group of healthy control including 68 blood donors with negative antibody were subjected to HLA-E genotyping. As a privilege, individuals hadn’t been vaccinated against COVID-19 and therefore naturally exposed to the SARS-CoV-2.ResultsThe absence of HLA-E*01:03 allele significantly decreases the odds of susceptibility to SARS-CoV-2 infection [p = 0.044; OR (95 %CI) = 0.530 (0.286 – 0.983)], suggesting that HLA-E*01:01 + HLA-E*01:01 genotype favors more protection against SARS-CoV-2 infection. HLA-E*01:03 + HLA-E*01:03 genotype was also significantly associated with more severe COVID-19 [p = 0.020; 2.606 (1.163 – 5.844)ConclusionHere, our observation about lower susceptibility of HLA-E*01:01 + HLA-E*01:01 genotype to COVID-19 could be clinical evidence in support of some previous studies suggesting that the lower affinity of HLA-E*01:01 to peptides derived from the leader sequence of MHC class Ia may instead shift its binding to virus-derived peptides, which then facilitates target recognition by restricted conventional CD8+ T cells and leads to efficient cytolysis. On the other hand, according to other studies, less reactivity of HLA-E*01:01 with NKG2A abrogates NK cells or T cells inhibition, which may also lead to a greater cytotoxicity against SARS-CoV-2 infected cells compared to HLA-E*01:03. Taken together given HLA-E polymorphisms, the data presented here may be useful in identifying more vulnerable individuals to COVID-19 for better care and management. Especially since along with other risk factors in patients, having HLA-E*01:03 + HLA-E*01:03 genotype may also be associated with the possibility of severe cases of the disease. |
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Keywords: | Coronavirus disease 2019 (COVID-19) HLA-E NK cell NKG2A Polymorphism SARS-CoV-2 Susceptibility CCP" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" Convalescent Plasma CI" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" Confidence interval CMV" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" Cytomegalovirus CTL" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" Cytotoxic T lymphocytes ELISA" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" Enzyme-linked immunosorbent assay HCV" },{" #name" :" keyword" ," $" :{" id" :" k9010" }," $$" :[{" #name" :" text" ," _" :" Hepatitis C virus HIV" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" Human immunodeficiency virus HLA" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" Human leukocyte antigen IgG" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" Immunoglobulin G MHC" },{" #name" :" keyword" ," $" :{" id" :" k0130" }," $$" :[{" #name" :" text" ," _" :" Major histocompatibility NK" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" Natural killer NKG2A" },{" #name" :" keyword" ," $" :{" id" :" k0150" }," $$" :[{" #name" :" text" ," _" :" Natural killer group 2A OR" },{" #name" :" keyword" ," $" :{" id" :" k0160" }," $$" :[{" #name" :" text" ," _" :" Odds ratio PCR" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" Polymerase chain reaction SARS-CoV" },{" #name" :" keyword" ," $" :{" id" :" k0180" }," $$" :[{" #name" :" text" ," _" :" Severe acute respiratory syndrome-coronavirus |
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