Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses.

Détails

ID Serval
serval:BIB_E2708B2CF397
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses.
Périodique
American journal of human genetics
Auteur(s)
Hammer C., Begemann M., McLaren P.J., Bartha I., Michel A., Klose B., Schmitt C., Waterboer T., Pawlita M., Schulz T.F., Ehrenreich H., Fellay J.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
05/11/2015
Peer-reviewed
Oui
Volume
97
Numéro
5
Pages
738-743
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DRβ1 haplotypes showed virus-specific patterns of humoral-response regulation. We observed an overlap between variants affecting the humoral response to influenza A and EBV and variants previously associated with autoimmune diseases related to these viruses. The results of this study emphasize the central and pathogen-specific role of HLA class II variation in the modulation of humoral immune response to viral antigens in humans.
Mots-clé
Adult, Autoimmune Diseases/genetics, Autoimmune Diseases/immunology, Autoimmune Diseases/pathology, Case-Control Studies, Female, Follow-Up Studies, Genome-Wide Association Study, Histocompatibility Antigens Class II/chemistry, Histocompatibility Antigens Class II/genetics, Histocompatibility Antigens Class II/immunology, Humans, Immunity, Humoral/immunology, Immunocompromised Host/immunology, Immunoglobulin G/blood, Male, Polymorphism, Single Nucleotide/genetics, Prognosis, Protein Conformation, Schizophrenia/genetics, Schizophrenia/immunology, Schizophrenia/pathology, Virus Diseases/genetics, Virus Diseases/immunology, Virus Diseases/virology, Viruses/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/10/2017 9:03
Dernière modification de la notice
15/07/2020 5:26
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