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Genetic Variability in NKG2 Receptors and Their Ligands: Associations with SARS-CoV-2 Infection and COVID-19 Severity

Year: 2025

Type: article

Abstract: Background: The emergence of the COVID-19 pandemic has accelerated research into diverse immune response mechanisms. One key area of interest is the regulation of cytotoxic activity by Natural Killer (NK) cells. These cells rely on a dynamic interplay between activating and inhibitory surface receptors that recognize specific ligands on target cells. Among these, receptors from the NKG2 family are particularly important, as maintaining their proper balance and function is essential for controlling NK cell cytotoxicity. Methods: In this study we employed qPCR to assess the genetic variability using single-nucleotide polymorphisms (SNPs) of NKG2A and NKG2D receptors and their ligands HLA-E and MICA/MICB. NKG2C deletion was determined by PCR-SSP, and serum-soluble levels of HLA-E and MICA/MICB molecules were measured by ELISA and Luminex methods. Results: Genotyping studies revealed that both NKG2A rs7301582 T and HLA-E rs1264457 A (HLA-E*01:01) alleles were predominant among infected individuals (OR = 2.21, p = 0.0258 and OR = 2.84, p = 0.0257, respectively). In contrast to MICB rs1065075 A, the MICA rs1051792 A (129Met) allele was most commonly found in hospitalized patients (OR = 14.95, p = 0.0114). The presence of the NKG2C del variant tended to be associated with an increased risk of SARS-CoV-2 infection (OR = 2.02, p = 0.0694). Moreover, higher concentrations of serum-soluble MICB was detected in infected individuals as compared to the control group (p = 0.008). Conclusions: Genetic variability of NK cell receptors and ligands as well as serum levels of their soluble forms showed associations with the risk of development of COVID-19 and the severity of its symptoms.

Source: Genes

DOI: 10.3390/genes16101193

Authors: Jagoda Siemaszko, Katarzyna Grad, Jerzy Świerkot, Katarzyna Bogunia-Kubik

Institutions: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, University of Wrocław, Wroclaw Medical University

Language: English

Topic: Immune Cell Function and Interaction

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,137