1. Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection
- Author
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Stefania Rassu, Roberto Perra, Sabrina Giglio, Simonetta Santus, Enrico Urru, S. Deidda, Antonella Palimodde, Claudia Murru, R. Porcella, Davide Firinu, Martina Loi, Angelo Restivo, Sara Lai, Alberto Lai, Marcello Campagna, Stefano Del Giacco, Goffredo Angioni, Daniele Schirru, Federico Meloni, William Cordeddu, Monica Vacca, Selene Cipri, Federica Cannas, F Alba, Paola Ragatzu, Luchino Chessa, Germano Orrù, Maurizio Melis, Andrea Perra, Marta Anna Kowalik, F. Coghe, Roberto Littera, Paola Congera, Silvia Deidda, Simona Onali, Francesco Pes, and Mauro Giovanni Carta
- Subjects
RNA viruses ,Male ,Viral Diseases ,Heredity ,Pulmonology ,Coronaviruses ,Genes, MHC Class I ,NK cells ,Ligands ,Immune Receptors ,Biochemistry ,Severity of Illness Index ,Group A ,Medical Conditions ,Gene Frequency ,Receptors, KIR ,Cellular types ,Receptor ,Immune Response ,Pathology and laboratory medicine ,education.field_of_study ,Immune System Proteins ,Multidisciplinary ,biology ,Immune cells ,Medical microbiology ,Middle Aged ,Killer Cells, Natural ,Genetic Mapping ,Infectious Diseases ,medicine.anatomical_structure ,Viruses ,White blood cells ,Medicine ,Female ,SARS CoV 2 ,Pathogens ,Antibody ,Research Article ,Signal Transduction ,Adult ,Cell biology ,Blood cells ,SARS coronavirus ,Science ,Immunology ,Population ,HLA-C Antigens ,Human leukocyte antigen ,Microbiology ,Natural killer cell ,Respiratory Disorders ,Immune system ,Genetics ,Immunogenetics ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Aged ,Medicine and health sciences ,Biology and life sciences ,SARS-CoV-2 ,business.industry ,Organisms ,Viral pathogens ,Immunity ,Case-control study ,Proteins ,COVID-19 ,Covid 19 ,Human Genetics ,Microbial pathogens ,Animal cells ,Haplotypes ,Case-Control Studies ,Respiratory Infections ,biology.protein ,business - Abstract
Background The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study’s focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. Methods KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. Results Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1–2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3–0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3–0.7), PM = 0.0005, PMC = 0.005]. Conclusions The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.
- Published
- 2021