Sex-Specific HLA Alleles Contribute to the Modulation of COVID-19 Severity.

Autor: Spartano S; Section of Genomic Medicine, Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy.; Complex Unit of Medical Genetics, Department of Laboratory and Infectivologic Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Faggiano MV; Section of Genomic Medicine, Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy.; Complex Unit of Medical Genetics, Department of Laboratory and Infectivologic Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Guidi G; Section of Infectious Diseases, Department of Safety and Bioethics, Catholic University of Sacred Heart, 00168 Rome, Italy.; Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., D'Ambrosio P; Section of Genomic Medicine, Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy.; Complex Unit of Medical Genetics, Department of Laboratory and Infectivologic Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Vaisfeld A; Section of Genomic Medicine, Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy.; Complex Unit of Medical Genetics, Department of Laboratory and Infectivologic Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Novelli A; Section of Genomic Medicine, Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy.; Complex Unit of Medical Genetics, Department of Laboratory and Infectivologic Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Falqui S; Section of Genomic Medicine, Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy.; Complex Unit of Medical Genetics, Department of Laboratory and Infectivologic Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Cingolani A; Section of Infectious Diseases, Department of Safety and Bioethics, Catholic University of Sacred Heart, 00168 Rome, Italy.; Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Lambertenghi L; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy., Visentin A; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy., Azzini A; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy., Righi E; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy., Trecarichi EM; Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, University 'Magna Graecia'-'R. Dulbecco', 88100 Catanzaro, Italy., Mazzitelli M; Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, University 'Magna Graecia'-'R. Dulbecco', 88100 Catanzaro, Italy., Coletti S; Chelonia SA, 6900 Lugano, Switzerland., Mous J; Chelonia SA, 6900 Lugano, Switzerland., Rademacher TW; Division of Infection and Immunity, University College London and Middlesex University, London WC1E 6BT, UK., Torti C; Section of Infectious Diseases, Department of Safety and Bioethics, Catholic University of Sacred Heart, 00168 Rome, Italy.; Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy.; Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences, University 'Magna Graecia'-'R. Dulbecco', 88100 Catanzaro, Italy., Tacconelli E; Infectious Diseases Division, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy.; Clinical Research Unit, German Center for Infectious Diseases, Tübingen University, 72074 Tübingen, Germany., Fantoni M; Section of Infectious Diseases, Department of Safety and Bioethics, Catholic University of Sacred Heart, 00168 Rome, Italy.; Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Cauda R; Section of Infectious Diseases, Department of Safety and Bioethics, Catholic University of Sacred Heart, 00168 Rome, Italy.; Unit of Infectious Diseases, Department of Medical and Surgical Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy., Tiziano FD; Section of Genomic Medicine, Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy.; Complex Unit of Medical Genetics, Department of Laboratory and Infectivologic Sciences, Policlinico 'A. Gemelli' Foundation, 00168 Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Dec 08; Vol. 25 (23). Date of Electronic Publication: 2024 Dec 08.
DOI: 10.3390/ijms252313198
Abstrakt: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, responsible for Coronavirus Disease 2019 (COVID-19), exhibits a spectrum of clinical manifestations, ranging from asymptomatic to severe pulmonary dysfunction or death. The variability in COVID-19 severity has largely been attributed to the host's genetic characteristics, suggesting a polygenic genetic architecture, without significant strong evidence of sex-related genetic differences. In this Italian retrospective case-control study, we investigated the association between COVID-19 severity (severe vs. asymptomatic/oligosymptomatic healed individuals) and HLA gene variants, analyzed by next-generation sequencing (NGS). We identified significant HLA alleles (according to the conventional nomenclature), SNPs and haplotypes in the HLA-B , -C , -F , -DQA1 , -DRB1 , and -DRB5 genes associated with COVID-19 severity. Interestingly, these variants showed biological sex-related effects. Also, we identified specific haplotypes associated with COVID-19 severity that are shared by different conventional HLA alleles, indicated here as "super-haplotypes". These haplotypes had a biological sex-specific impact on disease severity and markedly increased the risk of severe COVID-19 compared to the conventional HLA alleles (odds ratio of up to 15). Our data suggest that the revision of the current HLA nomenclature may help to identify variants with a stronger effect on disease susceptibility and that association studies could benefit from the stratification of patients by biological sex. If replicated in other disease models, these findings could help to define the functional diversity in immune response between sexes, also based on the HLA system. Finally, due to the global pandemic's mortality rate, we hypothesize here that SARS-CoV-2 may have acted as a natural selection trigger, leading to a drift in HLA allelic frequencies in the general population.
Databáze: MEDLINE
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