Muscle ischaemia associated with NXP2 autoantibodies: a severe subtype of juvenile dermatomyositis

Rheumatology (Oxford). 2018 May 1;57(5):873-879. doi: 10.1093/rheumatology/kex516.

Abstract

Objectives: Myositis-specific autoantibodies (MSAs) are increasingly used to delineate distinct subgroups of JDM. The aim of our study was to explore without a priori hypotheses whether MSAs are associated with distinct clinical-pathological changes and severity in a monocentric JDM cohort.

Methods: Clinical, biological and histological findings from 23 JDM patients were assessed. Twenty-six histopathological parameters were subjected to multivariate analysis.

Results: Autoantibodies included anti-NXP2 (9/23), anti-TIF1γ (4/23), anti-MDA5 (2/23), no MSAs (8/23). Multivariate analysis yielded two histopathological clusters. Cluster 1 (n = 11) showed a more severe and ischaemic pattern than cluster 2 (n = 12) assessed by: total score severity ⩾ 20 (100.0% vs 25.0%); visual analogic score ⩾6 (100.0% vs 25.0%); the vascular domain score >1 (100.0% vs 41.7%); microinfarcts (100% vs 58.3%); ischaemic myofibrillary loss (focal punched-out vacuoles) (90.9 vs 25%); and obvious capillary loss (81.8% vs 16.7). Compared with cluster 2, patients in cluster 1 had strikingly more often anti-NXP2 antibodies (7/11 vs 2/12), more pronounced muscle weakness, more gastrointestinal involvement and required more aggressive treatment. Furthermore, patients with anti-NXP2 antibodies, mostly assigned in the first cluster, also displayed more severe muscular disease, requiring more aggressive treatment and having a lower remission rate during the follow-up period.

Conclusion: Marked muscle ischaemic involvement and the presence of anti-NXP2 autoantibodies are associated with more severe forms of JDM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / immunology*
  • Adenosine Triphosphatases / metabolism
  • Autoantibodies / immunology*
  • Biomarkers / metabolism
  • Biopsy
  • DNA-Binding Proteins / immunology*
  • DNA-Binding Proteins / metabolism
  • Dermatomyositis / complications*
  • Dermatomyositis / immunology
  • Dermatomyositis / metabolism
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Ischemia / diagnosis
  • Ischemia / etiology*
  • Ischemia / immunology
  • Male
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / diagnostic imaging
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Biomarkers
  • DNA-Binding Proteins
  • Adenosine Triphosphatases
  • MORC3 protein, human