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

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