| Autor: |
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, Sergey V. Kozyrev, Maija-Leena Eloranta, Dag Leonard, Johanna Dahlqvist, Maria Lidén, Argyri Mathioudaki, Jennifer RS. Meadows, Jessika Nordin, Gunnel Nordmark, Antonella Notarnicola, Anna Tjärnlund, Maryam Dastmalchi, Daniel Eriksson, Øyvind Molberg, Fabiana H.G. Farias, Awat Jalal, Balsam Hanna, Helena Hellström, Tomas Husmark, Åsa Häggström, Anna Svärd, Thomas Skogh, Robert G. Cooper, Gerli Rosengren Pielberg, Anna Lobell, Åsa Karlsson, Eva Murén, Kerstin M. Ahlgren, Göran Andersson, Nils Landegren, Olle Kämpe, Peter Söderkvis |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
EBioMedicine, Vol 96, Iss , Pp 104804- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2023.104804 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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