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  • Review Article
  • Published:

Autoantibodies in myositis

Nature Reviews Rheumatology volume 14, pages 290–302 (2018)Cite this article

Subjects

Key Points

  • Myositis-specific autoantibodies (MSAs) are present in the majority of juvenile and adult cases of idiopathic inflammatory myopathy and are largely mutually exclusive.

  • Anti-TIF1γ, anti-NXP2 and anti-MDA5 antibodies are present in just over half of juvenile dermatomyositis cases, where they identify distinct subsets of disease.

  • In adults, anti-TIF1γ antibodies are associated with myositis-associated cancer, anti-HMGCR antibodies with statin-induced myosotis and anti-cN1A antibodies with inclusion body myositis.

  • The presence of anti-MDA5 antibodies in either myositis or clinically amyopathic dermatomyositis is a risk factor for rapidly progressive interstitial lung disease, particularly in Eastern Asian populations.

  • Interstitial lung disease is a prominent manifestation of antisynthetase syndrome, which is defined by the presence of antibodies to certain amino-acyl transfer RNA synthetases.

  • The discovery of novel myositis autoantigens is providing insights into pathogenesis and the links between autoimmunity and cancer.

Abstract

The discovery of novel autoantigen systems related to idiopathic inflammatory myopathies (collectively referred to as myositis) in adults and children has had major implications for the diagnosis and management of this group of diseases across a wide range of medical specialties. Traditionally, autoantibodies found in patients with myositis are described as being myositis-specific autoantibodies (MSAs) or myositis-associated autoantibodies (MAAs), depending on their prevalence in other, related conditions. However, certain MSAs are more closely associated with extramuscular manifestations, such as skin and lung disease, than with myositis itself. It is very rare for more than one MSA to coexist in the same individual, underpinning the potential to use MSAs to precisely define genetic and disease endotypes. Each MSA is associated with a distinctive pattern of disease or phenotype, which has implications for diagnosis and a more personalized approach to therapy. Knowledge of the function and localization of the autoantigenic targets for MSAs has provided key insights into the potential immunopathogenic mechanisms of myositis. In particular, evidence suggests that the alteration of expression of a myositis-related autoantigen by certain environmental influences or oncogenesis could be a pivotal event linking autoantibody generation to the development of disease.

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Figure 1: Myositis-specific autoantibody discovery and expected frequency in disease.
Figure 2: Tumorigenesis and postulated generation of myositis-specific autoantibodies.

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  1. Department of Pharmacy and Pharmacology, University of Bath, Bath, UK

    Neil J. McHugh & Sarah L. Tansley

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  1. Neil J. McHugh
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Both authors researched data for the article, made a substantial contribution to discussions of content, wrote the article and contributed to review and/or editing of the manuscript before submission.

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Correspondence to Neil J. McHugh.

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McHugh, N., Tansley, S. Autoantibodies in myositis. Nat Rev Rheumatol 14, 290–302 (2018). https://doi.org/10.1038/nrrheum.2018.56

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