title: Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum.
abstract: OBJECTIVE
  Autoantibodies against melanoma differentiation-associated protein 5 (MDA-5) have been described in several Asian dermatomyositis (DM) cohorts, often associated with amyopathic DM and rapidly progressive interstitial lung disease (ILD). A recent study of a DM cohort seen at a US dermatology clinic reports that MDA-5 autoantibodies are associated with a unique cutaneous phenotype. Given the widening spectrum of clinical findings, we evaluated the clinical features of anti-MDA-5-positive patients seen at a US myositis referral center.
  
  
  METHODS
  One hundred sixty DM patients were screened for MDA-5 autoantibodies by immunoprecipitation and antibody titers were analyzed in longitudinal serum samples. Anti-MDA-5-positive patients were evaluated for the presence of additional myositis autoantibodies. Patient clinical characteristics were compared by retrospective chart review.
  
  
  RESULTS
  MDA-5 was targeted in 11 (6.9%) of 160 patients with DM. Of these, 9 presented with a symmetric polyarthropathy, 6 demonstrated overt clinical myopathy, and 8 had ILD. Eight anti-MDA-5-positive patients exhibited the clinical attributes of the antisynthetase syndrome in the absence of Jo-1 or other antisynthetase autoantibodies. MDA-5 autoantibody titers did not correlate with clinical course.
  
  
  CONCLUSIONS
  MDA-5 autoantibodies are found in DM patients presenting with a symmetric polyarthritis, clinically similar to rheumatoid arthritis. These patients often have features of the antisynthetase syndrome, but in the absence of antisynthetase autoantibodies. Most anti-MDA-5-positive patients had overt clinical myopathy and ILD. The latter, while occasionally severe, typically resolved with immunosuppressive therapy. In this cohort, the MDA-5 phenotype is frequently a clinical mimic of the antisynthetase syndrome and is not associated with rapidly progressive ILD.
authors: Johns Hopkins University, Baltimore, Maryland.
authors: John C
authors: JC
authors: Hall
authors: Livia
authors: L
authors: Casciola-Rosen
authors: Lesly-Ann
authors: LA
authors: Samedy
authors: Jessie
authors: J
authors: Werner
authors: Kristie
authors: K
authors: Owoyemi
authors: Sonye K
authors: SK
authors: Danoff
authors: Lisa
authors: L
authors: Christopher-Stine
mesh_terms: D000328:Adult; D000604:Amino Acyl-tRNA Synthetases / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003882:Dermatomyositis / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D017563:Lung Diseases, Interstitial / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000175:diagnosis* / Q000276:immunology; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D000604:Amino Acyl-tRNA Synthetases