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Cross section of skeletal muscle under the microscope

Differences in genetic associations underpinning myositis subtypes

Novel genetic associations with myositis autoantibody subgroups and identification of functional variants provide mechanistic insights into disease pathogenesis.

Differences in genetic associations underpinning myositis subtypes

Full title

Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups.

 

Journal

Annals of the Rheumatic Diseases

 

Authors

S Rothwell, H Chinoy, JA Lamb, FW Miller, LG Rider, LR Wedderburn, NJ McHugh, IN Targoff, AL Mammen, ZE Betteridge, SL Tansley, J Bowes, J Vencovsky, CT Deakin, K Danko, V Limaye, A Selva-O’Callaghan, LM Pachman, AM Reed, O Molberg, O Benveniste, P Mathiesen, T Radstake, A Doria, JL De Bleecker, AT Lee, MG Hanna, PM Machado, WE Ollier, PK Gregersen, L Padyukov, TP O'Hanlon, RG Cooper, IE Lundberg, on behalf of the Myositis Genetics Consortium (MYOGEN)

 

Novel genetic associations with myositis autoantibody subgroups and identification of functional variants provide mechanistic insights into disease pathogenesis.

The idiopathic inflammatory myopathies (IIM), known collectively as myositis, are a spectrum of rare autoimmune diseases characterised by muscle weakness and systemic organ involvement.

A number of different autoantibodies can be detected in myositis patients that correlate with clinical features of disease and response to treatment. The strongest genetic factor for IIM is within the human leukocyte antigen (HLA) region in autoantibody subgroups.

In this study, we aimed to identify novel risk variants in the HLA region associated with IIM autoantibodies.

We show that there are both shared and distinct strong HLA associations with certain autoantibodies. We identify specific amino acids within HLA molecules that may be functionally important in disease pathogenesis.

This study shows for the first time genetic differences between adult- and juvenile-onset patients, with anti-TIF1 autoantibodies suggesting distinct aetiologies in this subgroup.

As autoantibodies in myositis correlate with specific clinical features of disease, understanding genetic risk underlying development of certain autoantibody profiles has implications for patient management.

Key facts

  • Myositis autoantibodies correlate with specific clinical features of disease.
  • The strongest genetic risk with myositis autoantibodies are with genes in the human leukocyte antigen (HLA) region.
  • Different autoantibodies have distinct HLA associations.
  • Specific amino acids within HLA molecules confer the strongest risk.
  • There are genetic differences between adult- and juvenile-onset patients.

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Footnotes

Authors affiliated to The University of Manchester are supported in part by: Myositis UK, The Myositis Association, Versus Arthritis, Medical Research Council and the NIHR Biomedical Research Centre Funding Scheme. For a full list of funders and acknowledgements, please see the published manuscript.