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Analysis of Killer Cell Immunoglobulin-Like Receptor Genes and Their HLA Ligands in Inflammatory Bowel Diseases.

ABSTRACT: Genetic studies have illustrated that killer cell immunoglobulin-like receptor (KIR) genes could participate in various autoimmune disorders. We aimed to clarify the role of KIR genes, HLA ligands, HLA-KIR interactions, and their genotypes in inflammatory bowel disease (IBD) susceptibility. The study population was composed of 183 IBD subjects, comprising 100 ulcerative colitis (UC) patients, 83 Crohn's disease (CD) patients, and 274 healthy subjects. Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to evaluate the absence or presence of the 15 KIR genes, 5 HLA class I ligands, and 2 pseudogenes. We did not find any significant difference in allele frequency of KIRs and pseudogenes between IBD patients and healthy controls. In the case of HLA genes, there was a significant difference in HLA-B-Bw4Thr80 frequency between UC patients and healthy controls (P = 0.03, OR = 0.06, 95%CI = 0.008-0.4). Furthermore, we found a significant difference in HLA-C1Asn80 frequency between CD patients and healthy controls (P = 0.04, OR = 0.49, 95% CI = 0.3-0.8). In the full-array combination of KIR genes, there was no significant frequency difference between UC patients and healthy controls, while two KIR genotypes showed a significant susceptible association with CD. Our data do not support a strong role of NK cells in IBD susceptibility, but it does not rule out a role for KIR variability in IBD patients. However, there are some protective associations such as Bw4 alleles; these associations may be due to the interaction of the alleles to TCRs rather than KIRs.

SUBMITTER: Beigmohammadi F

PROVIDER: S-EPMC7520679 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Analysis of Killer Cell Immunoglobulin-Like Receptor Genes and Their HLA Ligands in Inflammatory Bowel Diseases.

Beigmohammadi Fereshteh F Mahmoudi Mahdi M Karami Jafar J Ahmadzadeh Nooshin N Ebrahimi-Daryani Nasser N Rezaei Nima N

Journal of immunology research 20200919

Genetic studies have illustrated that killer cell immunoglobulin-like receptor (KIR) genes could participate in various autoimmune disorders. We aimed to clarify the role of KIR genes, HLA ligands, HLA-KIR interactions, and their genotypes in inflammatory bowel disease (IBD) susceptibility. The study population was composed of 183 IBD subjects, comprising 100 ulcerative colitis (UC) patients, 83 Crohn's disease (CD) patients, and 274 healthy subjects. Polymerase chain ...[more]

PMID: 33015197

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Project description:Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-2019 (COVID-19) in some individuals, while the majority remain asymptomatic. Natural killer (NK) cells play an essential role in antiviral defense. NK cell maturation and function are regulated mainly by highly polymorphic killer cell immunoglobulin-like receptors (KIR) and cognate HLA class I ligands. Herein, we tested our hypothesis that the individualized KIR and HLA class I ligand combinations that control NK cell function determine the outcome of SARS-CoV-2 infection. Methods: We characterized KIR and HLA genes in 200 patients hospitalized for COVID-19 and 195 healthy general population controls. Results: The KIR3DL1+HLA-Bw4+ [Odds ratio (OR) = 0.65, p = 0.03] and KIR3DL2+HLA-A3/11+ (OR = 0.6, p = 0.02) combinations were encountered at significantly lower frequency in COVID-19 patients than in the controls. Notably, 40% of the patients lacked both of these KIR+HLA+ combinations compared to 24.6% of the controls (OR = 2.04, p = 0.001). Additionally, activating receptors KIR2DS1+KIR2DS5+ are more frequent in patients with severe COVID-19 than patients with mild disease (OR = 1.8, p = 0.05). Individuals carrying KIR2DS1+KIR2DS5+ genes but missing either KIR3DL1+HLA-Bw4+ combination (OR = 1.73, p = 0.04) or KIR3DL2+HLA-A3/11+ combination (OR = 1.75, p = 0.02) or both KIR3DL1+HLA-Bw4+ and KIR2DL2+HLA-A3/11+ combinations (OR = 1.63, p = 0.03) were more frequent in the COVID-19 cohort compared to controls. Conclusions: The absence of KIR3DL1+HLA-Bw4+ and KIR3DL2+HLA-A3/11+ combinations presumably yields inadequate NK cell maturation and reduces anti-SARS-CoV-2 defense, causing COVID-19. An increased frequency of KIR2DS1+KIR2DS5+ in severe COVID-19 patients suggests vigorous NK cell response triggered via these activating receptors and subsequent production of exuberant inflammatory cytokines responsible for severe COVID-19. Our results demonstrate that specific KIR-HLA combinations that control NK cell maturation and function are underlying immunogenetic variables that determine the dual role of NK cells in mediating beneficial antiviral and detrimental pathologic action. These findings offer a framework for developing potential host genetic biomarkers to distinguish individuals prone to COVID-19.

Dataset Information

Analysis of Killer Cell Immunoglobulin-Like Receptor Genes and Their HLA Ligands in Inflammatory Bowel Diseases.

Publications

Analysis of Killer Cell Immunoglobulin-Like Receptor Genes and Their HLA Ligands in Inflammatory Bowel Diseases.

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