The effects of killer cell immunoglobulin-like receptor (KIR) genes on susceptibility to severe COVID-19 in the Iranian population

TL;DR

This study explores how specific KIR genes influence the severity of COVID-19 in Iranians, finding some genes may protect against severe disease.

Contribution

The study identifies specific KIR genes and haplotypes associated with mild or severe COVID-19 in the Iranian population.

Findings

KIR2DS1 and KIR2DS2 genes are more common in mild cases, suggesting a protective role.

KIR3DL3 and KIR2DS4 are more frequent in severe cases, indicating increased risk.

B haplotype is linked to milder disease, while haplotype A is associated with severity.

Abstract

Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Killer-cell immunoglobulin-like receptor (KIR) family. We aimed to investigate the impact of possessing certain KIR genes and genotypes on COVID19 severity in Iranians. KIR genotyping was performed on 394 age/sex matched Iranians with no underlying conditions who developed mild and severe COVID- 19. The presence and/or absence of 11 KIR genes were determined using the PCR with sequence specific primers (PCR-SSP).

Patients with mild symptoms had higher frequency ofKIR2DS1 (p = 0.004) and KIR2DS2 (p = 0.017) genes compared to those with severe disease. While KIR3DL3 and deleted variant of KIR2DS4 occurred more frequently in patients who developed a severe form of the disease. In this study, a significant increase of and B haplotype was observed in the Mild group compared to the Severe group (respectively, p = 0.002 and p = 0.02). Also, the prevalence of haplotype A was significantly higher in the Severe group than in the Mild group (p = 0.02).

These results suggest that the KIR2DS1, KIR2DS, and B haplotype maybe have a protective effect against COVID-19 severity. The results also suggest the inhibitory gene KIR2DL3 and haplotype A are risk factors for the severity of COVID-19.

The online version contains supplementary material available at 10.1186/s12865-024-00631-1.

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