EBioMedicine (Oct 2023)

Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathiesResearch in context

  • 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 Holmqvist,
  • Matteo Bianchi,
  • Leonid Padyukov,
  • Ingrid E. Lundberg,
  • Lina-Marcela Diaz-Gallo,
  • Matteo Bianchi,
  • Sergey V. Kozyrev,
  • Johanna K. Sandling,
  • Lars Rönnblom,
  • Maija-Leena Eloranta,
  • Ann-Christine Syvänen,
  • Dag Leonard,
  • Johanna Dahlqvist,
  • Maria Lidén,
  • Argyri Mathioudaki,
  • Jennifer RS. Meadows,
  • Jessika Nordin,
  • Gunnel Nordmark,
  • Ingrid E. Lundberg,
  • Antonella Notarnicola,
  • Leonid Padyukov,
  • Anna Tjärnlund,
  • Maryam Dastmalchi,
  • Daniel Eriksson,
  • Øyvind Molberg,
  • Helena Andersson,
  • Kerstin Lindblad-Toh,
  • Fabiana H.G. Farias,
  • Marie Wahren-Herlenius,
  • Awat Jalal,
  • Balsam Hanna,
  • Helena Hellström,
  • Tomas Husmark,
  • Åsa Häggström,
  • Anna Svärd,
  • Thomas Skogh,
  • Louise Pyndt Diederichsen,
  • Janine A. Lamb,
  • Simon Rothwell,
  • Hector Chinoy,
  • Robert G. Cooper,
  • Kerstin Lindblad-Toh,
  • Gerli Rosengren Pielberg,
  • Anna Lobell,
  • Åsa Karlsson,
  • Eva Murén,
  • Kerstin M. Ahlgren,
  • Lars Rönnblom,
  • Maija-Leena Eloranta,
  • Göran Andersson,
  • Nils Landegren,
  • Olle Kämpe,
  • Peter Söderkvis

Journal volume & issue
Vol. 96
p. 104804

Abstract

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Summary: 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.

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