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

Valérie Leclair*, Angeles S Galindo-Feria, Simon Rothwell, Olga Kryštůfková, Sepehr Sarrafzadeh Zargar, Herman Mann, Louise Pyndt Diederichsen, Helena Andersson, Martin Klein, Sarah Tansley, Lars Rönnblom, Kerstin Lindblad-Toh, Ann-Christine Syvänen, Marie Wahren-Herlenius, Johanna K Sandling, Neil McHugh, Janine A Lamb, Jiri Vencovský, Hector Chinoy, Marie HolmqvistMatteo Bianchi, Leonid Padyukov, Ingrid E Lundberg, Lina-Marcela Diaz-Gallo*, Dissect Consortium and The Immunoarray Development Consortium

*Corresponding author af dette arbejde
6 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
Artikelnummer104804
TidsskriftEBioMedicine
Vol/bind96
DOI
StatusUdgivet - okt. 2023

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