Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathies

. 2023 Oct ; 96 () : 104804. [epub] 20230926

Jazyk angličtina Země Nizozemsko Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid37769433

Grantová podpora
MR/N003322/1 Medical Research Council - United Kingdom

Odkazy

PubMed 37769433
PubMed Central PMC10550566
DOI 10.1016/j.ebiom.2023.104804
PII: S2352-3964(23)00370-5
Knihovny.cz E-zdroje

BACKGROUND: In patients with idiopathic inflammatory myopathies (IIM), autoantibodies are associated with specific clinical phenotypes suggesting a pathogenic role of adaptive immunity. We explored if autoantibody profiles are associated with specific HLA genetic variants and clinical manifestations in IIM. METHODS: We included 1348 IIM patients and determined the occurrence of 14 myositis-specific or -associated autoantibodies. We used unsupervised cluster analysis to identify autoantibody-defined subgroups and logistic regression to estimate associations with clinical manifestations, HLA-DRB1, HLA-DQA1, HLA-DQB1 alleles, and amino acids imputed from genetic information of HLA class II and I molecules. FINDINGS: We identified eight subgroups with the following dominant autoantibodies: anti-Ro52, -U1RNP, -PM/Scl, -Mi2, -Jo1, -Jo1/Ro52, -TIF1γ or negative for all analysed autoantibodies. Associations with HLA-DRB1∗11, HLA-DRB1∗15, HLA-DQA1∗03, and HLA-DQB1∗03 were present in the anti-U1RNP-dominated subgroup. HLA-DRB1∗03, HLA-DQA1∗05, and HLA-DQB1∗02 alleles were overrepresented in the anti-PM/Scl and anti-Jo1/Ro52-dominated subgroups. HLA-DRB1∗16, HLA-DRB1∗07 alleles were most frequent in anti-Mi2 and HLA-DRB1∗01 and HLA-DRB1∗07 alleles in the anti-TIF1γ subgroup. The HLA-DRB1∗13, HLA-DQA1∗01 and HLA-DQB1∗06 alleles were overrepresented in the negative subgroup. Significant signals from variations in class I molecules were detected in the subgroups dominated by anti-Mi2, anti-Jo1/Ro52, anti-TIF1γ, and the negative subgroup. INTERPRETATION: Distinct HLA class II and I associations were observed for almost all autoantibody-defined subgroups. The associations support autoantibody profiles use for classifying IIM which would likely reflect underlying pathogenic mechanisms better than classifications based on clinical symptoms and/or histopathological features. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

Center for Rheumatology and Spine Diseases Copenhagen University Hospital Rigshospitalet Copenhagen Denmark; Department of Rheumatology Odense University Hospital Odense Denmark

Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Faculty of Biology Medicine and Health University of Manchester Manchester United Kingdom

Clinical Epidemiology Division Department Medicine Solna Karolinska Institutet Karolinska University Hospital Stockholm Sweden; Division of Rheumatology Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden

Clinical Epidemiology Division Department Medicine Solna Karolinska Institutet Karolinska University Hospital Stockholm Sweden; Division of Rheumatology Jewish General Hospital Lady Davis Institute Montreal Canada

Department of Life Sciences University of Bath Bath United Kingdom

Department of Medical Sciences Rheumatology Uppsala University Uppsala Sweden

Department of Rheumatology Oslo University Hospital Oslo Norway

Department of Rheumatology Salford Royal Hospital Northern Care Alliance NHS Foundation Trust Manchester Academic Health Science Centre Salford United Kingdom; Division of Musculoskeletal and Dermatological Sciences Faculty of Biology Medicine and Health The University of Manchester Manchester United Kingdom

Division of Rheumatology Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden; Broegelmann Research Laboratory Department of Clinical Science University of Bergen Norway

Division of Rheumatology Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden; Center for Molecular Medicine Karolinska Institutet and Karolinska University Hospital Stockholm Sweden

Epidemiology and Public Health Group Faculty of Biology Medicine and Health University of Manchester United Kingdom

Institute of Rheumatology and Department of Rheumatology 1st Medical Faculty Charles University Prague Czech Republic

Science for Life Laboratory Department of Medical Biochemistry and Microbiology Uppsala University Uppsala Sweden

Science for Life Laboratory Department of Medical Biochemistry and Microbiology Uppsala University Uppsala Sweden; Broad Institute of MIT and Harvard Cambridge MA Unite States of America

Science for Life Laboratory Uppsala University Department of Medical Sciences Molecular Precision Medicine Uppsala Sweden

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