Publication date: Jul 03, 2025
Natural killer (NK) cells play a key role in the innate immune response against viral infections. Their activity is regulated by a balance of activating and inhibitory signals, which are modulated by interactions with HLA class I molecules, including HLA-E. The HLA-B 21M/T dimorphism influences the availability of HLA-B leader peptides that stabilize HLA-E expression and modulate NK cell function via the NKG2A/CD94 receptor. To investigate the association between the HLA-B -21M/T dimorphism and the clinical severity of COVID-19, we analyzed a cohort of hospitalized patients with primary SARS-CoV-2 infection, who were genotyped for the HLA-B -21M/T dimorphism. Clinical data, lymphocyte counts, the neutrophil-to-lymphocyte ratio (NLR), and inflammatory markers were compared across genotypes. Contrary to previous studies suggesting a protective effect of the M/M genotype, we found no significant association between the HLA-B -21M/T dimorphism and COVID-19 severity, lymphocyte parameters, or inflammatory biomarkers. Our findings do not support a role for the HLA-B -21M/T dimorphism in modulating COVID-19 outcomes. These results underscore the complexity of NK cell regulation and highlight the need for integrative studies combining genetic, immunological, and functional data to better understand host factors influencing disease progression.
Open Access PDF
| Concepts | Keywords |
|---|---|
| Cd94 | Adult |
| Host | Aged |
| Immunological | COVID-19 |
| Viral | COVID-19 |
| Female | |
| Genotype | |
| HLA-B Antigens | |
| HLA-B Antigens | |
| HLA-E | |
| Humans | |
| Killer Cells, Natural | |
| Male | |
| Middle Aged | |
| NK cells | |
| SARS-CoV-2 |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | role |
| disease | MESH | COVID-19 |
| disease | IDO | innate immune response |
| disease | MESH | viral infections |
| drug | DRUGBANK | Isoxaflutole |
| disease | IDO | cell |
| pathway | REACTOME | SARS-CoV-2 Infection |
| drug | DRUGBANK | Tropicamide |
| disease | IDO | host |
| disease | MESH | disease progression |
| drug | DRUGBANK | Coenzyme M |
| disease | IDO | susceptibility |
| disease | MESH | infection |
| pathway | REACTOME | Immune System |
| drug | DRUGBANK | Methionine |
| drug | DRUGBANK | L-Threonine |
| disease | MESH | infectious diseases |
| disease | MESH | asthma |
| pathway | KEGG | Asthma |
| disease | MESH | Obesity |
| disease | MESH | Myocardial Infarction |
| disease | MESH | Heart Failure |
| disease | MESH | Hemiplegia |
| disease | MESH | COPD |
| disease | MESH | Gastric Ulcer |
| disease | MESH | Neoplasm |
| disease | MESH | Lymphoma |
| disease | IDO | immunosuppression |
| disease | MESH | hypertension |
| disease | MESH | chronic kidney disease |