Influence of HLA-G 3' Untranslated Region Haplotypes and SNP +3422 Gene Variants as Host Genetic Factors on the Outcomes of SARS-CoV-2 Infection During Acute and Post-Acute Phases in a German Cohort.

Autor: Rohn H; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany., Elischer F; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Larbig L; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Jansen S; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany., Schramm S; Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Otte M; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany., Konik M; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany., Paniskaki K; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany., Weber P; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany., Reinold J; Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Gäckler A; Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Krawczyk A; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Wilde B; Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Trilling M; Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Institute for the Research on Translational HIV and AIDS-Associated Diseases Research, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Michita RT; Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA., Möhlendick B; Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Siffert W; Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Brenner T; Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Dinse H; Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, Essen, Germany., Skoda EM; Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, Essen, Germany., Horn PA; Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Witzke O; Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, Essen, Germany., Rebmann V; Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Jazyk: angličtina
Zdroj: HLA [HLA] 2024 Dec; Vol. 104 (6), pp. e15799.
DOI: 10.1111/tan.15799
Abstrakt: HLA-G, an important immune-checkpoint (IC) molecule that exerts inhibitory signalling on immune effector cells, has been suggested to represent a key player in regulating the immune response to Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2). Since specific single-nucleotide polymorphisms (SNP) in the HLA-G 3'untranslated region (UTR), which arrange as haplotypes, are crucial for the regulation of HLA-G expression, we analysed the contribution of these genetic variants as host factors in SARS-CoV-2 infection during acute and post-acute phases. HLA-G gene polymorphisms in the 3'UTR were investigated by sequencing in an unvaccinated Coronavirus Disease 2019 (COVID-19) cohort during acute SARS-CoV-2 infection (N = 505) and in the post-acute phase (N = 253). The HLA-G 3'UTR haplotype known as UTR-3 (p = 0.002) and the variant rs17875408 (also known as +3422) T variant (p = 0.004) are independent prognostic risk factors for fatal COVID-19. The +3422T variant (p = 0.006) predicted also the early loss of neutralising SARS-CoV-2 antibodies. In addition, the HLA-G 3'UTR haplotype UTR-7 (p = 0.023) emerged as an independent prognostic factor for increased susceptibility to Long-COVID symptoms after SARS-CoV-2 infection. Our study highlights that due to the variability of the 3'UTR genetic background, HLA-G has the potential to contribute to the progression of SARS-CoV-2 infection, extending to the development of Long-COVID symptoms, despite the likely alterations in the microenvironment and associated HLA-G-specific regulatory elements over the course of the disease. By spotlighting HLA-G, the importance of the genetic background of IC and their pivotal role in modulating immune responses during and after COVID-19 are emphasised.
(© 2024 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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