tetano
Editor, Senior Moderator
J Immunol Res
. 2025 May 12:2025:6691437.
doi: 10.1155/jimr/6691437. eCollection 2025. The Impact of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen-E, Human Leukocyte Antigen-G Polymorphisms on Innate Immunity and COVID-19 Severity
Cigdem Kekik[SUP] 1 [/SUP], Sonay Temurhan[SUP] 1 [/SUP], Yeliz Ogret[SUP] 1 [/SUP], Behnoush Nasr Zanjani[SUP] 2 [/SUP], Demet Kıvanc[SUP] 1 [/SUP], Fatma Savran Oguz[SUP] 1 [/SUP], Murat Kose[SUP] 3 [/SUP], Fatma Betul Oktelik[SUP] 4 [/SUP], Gunnur Deniz[SUP] 4 [/SUP]
Affiliations
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spans a spectrum of symptoms, ranging from mild respiratory issues to severe outcomes like pneumonia, acute respiratory distress syndrome, and fatality. Natural killer (NK) cells, governed by killer cell immunoglobulin-like receptors (KIRs), play a pivotal role in directly combating viral infections. Emerging studies indicate a decline in NK cell numbers and heightened NKG2A expression in infected individuals. Objective: This study focuses on genotyping human leukocyte antigen (HLA)-E, HLA-G, and KIR in SARS-CoV-2-positive individuals, comparing data between those with mild and moderate/severe symptoms. The cohort comprised 100 COVID-19-positive patients and 100 healthy volunteers, both groups subjected to DNA isolation and genotyping using sequence-based sequencing. Results: In 97 COVID-19-positive patients (52 mild, 24 moderate, and 21 severe) and 100 healthy volunteers, the study revealed protective associations with inhibitory alleles (KIR2DL1, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, and pseudo-alleles like KIR3DP1 [SUP]∗[/SUP] 003). Conversely, predisposing factors included activator alleles (KIR2DS2, KIR3DS1) and pseudo-alleles (KIR3DP [SUP]∗[/SUP] 001/002). The G [SUP]∗[/SUP] 01:04 allele and G [SUP]∗[/SUP] 01:04-G [SUP]∗[/SUP] 01:04 genotype emerged as protective, while the HLA-E [SUP]∗[/SUP] 01:03-HLA-E [SUP]∗[/SUP] 01:03 genotype may negatively impact disease prognosis. Conversely, the HLA-E [SUP]∗[/SUP] 01:01-HLA-E [SUP]∗[/SUP] 01:03 and HLA-E [SUP]∗[/SUP] 01:01-HLA-E [SUP]∗[/SUP] 01:01 genotypes may confer protection. Conclusion: Genetic variations in KIR, HLA-E, and HLA-G are associated with susceptibility and resistance to severe COVID-19 outcomes. This elucidates the intricate interplay of NK cells and immune-related genes, offering insights into potential therapeutic avenues and personalized approaches.
Keywords: COVID-19; HLA-G genotype; Human Leukocyte Antigen-E (HLA-E); killer cell immunoglobulin-like receptor (KIR); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
. 2025 May 12:2025:6691437.
doi: 10.1155/jimr/6691437. eCollection 2025. The Impact of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen-E, Human Leukocyte Antigen-G Polymorphisms on Innate Immunity and COVID-19 Severity
Cigdem Kekik[SUP] 1 [/SUP], Sonay Temurhan[SUP] 1 [/SUP], Yeliz Ogret[SUP] 1 [/SUP], Behnoush Nasr Zanjani[SUP] 2 [/SUP], Demet Kıvanc[SUP] 1 [/SUP], Fatma Savran Oguz[SUP] 1 [/SUP], Murat Kose[SUP] 3 [/SUP], Fatma Betul Oktelik[SUP] 4 [/SUP], Gunnur Deniz[SUP] 4 [/SUP]
Affiliations
- PMID: 40391199
- PMCID: PMC12088842
- DOI: 10.1155/jimr/6691437
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spans a spectrum of symptoms, ranging from mild respiratory issues to severe outcomes like pneumonia, acute respiratory distress syndrome, and fatality. Natural killer (NK) cells, governed by killer cell immunoglobulin-like receptors (KIRs), play a pivotal role in directly combating viral infections. Emerging studies indicate a decline in NK cell numbers and heightened NKG2A expression in infected individuals. Objective: This study focuses on genotyping human leukocyte antigen (HLA)-E, HLA-G, and KIR in SARS-CoV-2-positive individuals, comparing data between those with mild and moderate/severe symptoms. The cohort comprised 100 COVID-19-positive patients and 100 healthy volunteers, both groups subjected to DNA isolation and genotyping using sequence-based sequencing. Results: In 97 COVID-19-positive patients (52 mild, 24 moderate, and 21 severe) and 100 healthy volunteers, the study revealed protective associations with inhibitory alleles (KIR2DL1, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, and pseudo-alleles like KIR3DP1 [SUP]∗[/SUP] 003). Conversely, predisposing factors included activator alleles (KIR2DS2, KIR3DS1) and pseudo-alleles (KIR3DP [SUP]∗[/SUP] 001/002). The G [SUP]∗[/SUP] 01:04 allele and G [SUP]∗[/SUP] 01:04-G [SUP]∗[/SUP] 01:04 genotype emerged as protective, while the HLA-E [SUP]∗[/SUP] 01:03-HLA-E [SUP]∗[/SUP] 01:03 genotype may negatively impact disease prognosis. Conversely, the HLA-E [SUP]∗[/SUP] 01:01-HLA-E [SUP]∗[/SUP] 01:03 and HLA-E [SUP]∗[/SUP] 01:01-HLA-E [SUP]∗[/SUP] 01:01 genotypes may confer protection. Conclusion: Genetic variations in KIR, HLA-E, and HLA-G are associated with susceptibility and resistance to severe COVID-19 outcomes. This elucidates the intricate interplay of NK cells and immune-related genes, offering insights into potential therapeutic avenues and personalized approaches.
Keywords: COVID-19; HLA-G genotype; Human Leukocyte Antigen-E (HLA-E); killer cell immunoglobulin-like receptor (KIR); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).