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

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

Leclair, Valerie (author): Karolinska Institutet

Galindo-Feria, Angeles S. (author): Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.

Rothwell, Simon (author): Univ Manchester, Ctr Musculoskeletal Res, Fac Biol Med & Hlth, Ctr Genet & Genom Versus Arthrit, Manchester, England.

Krystufkova, Olga (author)

Zargar, Sepehr Sarrafzadeh (author): Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.

Mann, Herman (author): Charles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Med Fac 1, Dept Rheumatol, Prague, Czech Republic.

Diederichsen, Louise Pyndt (author): Copenhagen Univ Hosp, Rigshosp, Ctr Rheumatol & Spine Dis, Copenhagen, Denmark.;Odense Univ Hosp, Dept Rheumatol, Odense, Denmark.

Andersson, Helena (author): Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway.

Klein, Martin (author): Charles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Med Fac 1, Dept Rheumatol, Prague, Czech Republic.

Tansley, Sarah (author): Univ Bath, Dept Life Sci, Bath, Avon, England.

Rönnblom, Lars (author): Uppsala universitet,Reumatologi,The Dissect Consortium and The Immunoarray Development Consortium

Lindblad-Toh, Kerstin (author): Uppsala 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

Syvänen, Ann-Christine, 1950- (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär precisionsmedicin,The Dissect Consortium and The Immunoarray Development Consortium

Wahren-Herlenius, Marie (author): Karolinska Institutet

Sandling, Johanna K. (author): Uppsala universitet,Reumatologi,The Dissect Consortium and The Immunoarray Development Consortium

McHugh, Neil (author): Univ Bath, Dept Life Sci, Bath, Avon, England.

Lamb, Janine A. (author): Univ Manchester, Fac Biol Med & Hlth, Epidemiol & Publ Hlth Grp, Manchester, Lancs, England.

Vencovsky, Jiri (author): Charles Univ Prague, Fac Med 1, Inst Rheumatol, Prague, Czech Republic.;Charles Univ Prague, Med Fac 1, Dept Rheumatol, Prague, Czech Republic.

Chinoy, Hector (author): Northern 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.

Holmqvist, Marie (author): Karolinska Institutet

Bianchi, Matteo (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,The Dissect Consortium and The Immunoarray Development Consortium

Padyukov, Leonid (author): Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.

Lundberg, Ingrid E. (author): Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.

Diaz-Galloc, Lina-Marcela (author): Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.

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Karolinska Institutet Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (creator_code:org_t)

Elsevier, 2023
2023
English.
In: EBioMedicine. - : Elsevier. - 2352-3964. ; 96

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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/).

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)

Keyword

Autoantibody
HLA
Idiopathic inflammatory myopathy
Myositis

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

Articles in the publication: EBioMedicine

By the university: Uppsala University; Karolinska Institutet

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