Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathies
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
MR/N003322/1
Medical Research Council - United Kingdom
PubMed
37769433
PubMed Central
PMC10550566
DOI
10.1016/j.ebiom.2023.104804
PII: S2352-3964(23)00370-5
Knihovny.cz E-zdroje
- Klíčová slova
- Autoantibody, HLA, Idiopathic inflammatory myopathy, Myositis,
- MeSH
- alely MeSH
- autoprotilátky * genetika MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- haplotypy MeSH
- HLA-DRB1 řetězec genetika MeSH
- lidé MeSH
- myozitida * genetika imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- autoprotilátky * MeSH
- HLA-DRB1 řetězec MeSH
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.
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
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