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  • Leclair, ValerieKarolinska Institutet (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier,2023
  • electronicrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:uu-516917
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-516917URI
  • https://doi.org/10.1016/j.ebiom.2023.104804DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:154131097URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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,-TIF1 gamma 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-TIF1 gamma 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-TIF1 gamma, 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. Copyright (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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  • Galindo-Feria, Angeles S.Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (author)
  • Rothwell, SimonUniv Manchester, Ctr Musculoskeletal Res, Fac Biol Med & Hlth, Ctr Genet & Genom Versus Arthrit, Manchester, England. (author)
  • Krystufkova, Olga (author)
  • Zargar, Sepehr SarrafzadehKarolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (author)
  • Mann, HermanCharles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Med Fac 1, Dept Rheumatol, Prague, Czech Republic. (author)
  • Diederichsen, Louise PyndtCopenhagen Univ Hosp, Rigshosp, Ctr Rheumatol & Spine Dis, Copenhagen, Denmark.;Odense Univ Hosp, Dept Rheumatol, Odense, Denmark. (author)
  • Andersson, HelenaOslo Univ Hosp, Dept Rheumatol, Oslo, Norway. (author)
  • Klein, MartinCharles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Med Fac 1, Dept Rheumatol, Prague, Czech Republic. (author)
  • Tansley, SarahUniv Bath, Dept Life Sci, Bath, Avon, England. (author)
  • Rönnblom, LarsUppsala universitet,Reumatologi,The Dissect Consortium and The Immunoarray Development Consortium(Swepub:uu)larsronn (author)
  • Lindblad-Toh, KerstinUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA USA.,The Dissect Consortium and The Immunoarray Development Consortium(Swepub:uu)kerli865 (author)
  • Syvänen, Ann-Christine,1950-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär precisionsmedicin,The Dissect Consortium and The Immunoarray Development Consortium(Swepub:uu)anncsyva (author)
  • Wahren-Herlenius, MarieKarolinska Institutet (author)
  • Sandling, Johanna K.Uppsala universitet,Reumatologi,The Dissect Consortium and The Immunoarray Development Consortium(Swepub:uu)josan062 (author)
  • McHugh, NeilUniv Bath, Dept Life Sci, Bath, Avon, England. (author)
  • Lamb, Janine A.Univ Manchester, Fac Biol Med & Hlth, Epidemiol & Publ Hlth Grp, Manchester, Lancs, England. (author)
  • Vencovsky, JiriCharles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Med Fac 1, Dept Rheumatol, Prague, Czech Republic. (author)
  • Chinoy, HectorNorthern Care Alliance NHS Fdn Trust, Salford Royal Hosp, Manchester Acad Hlth Sci Ctr, Dept Rheumatol, Salford, Lancs, England.;Univ Manchester, Fac Biol Med & Hlth, Div Musculoskeletal & Dermatol Sci, Manchester, Lancs, England. (author)
  • Holmqvist, MarieKarolinska Institutet (author)
  • Bianchi, MatteoUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,The Dissect Consortium and The Immunoarray Development Consortium(Swepub:uu)matbi944 (author)
  • Padyukov, LeonidKarolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (author)
  • Lundberg, Ingrid E.Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (author)
  • Diaz-Galloc, Lina-MarcelaKarolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (author)
  • Karolinska InstitutetKarolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (creator_code:org_t)

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  • In:EBioMedicine: Elsevier962352-3964

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