title: Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study.
abstract: BACKGROUND
  The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM).
  
  
  METHODS
  Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist).
  
  
  RESULTS
  Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease.
  
  
  CONCLUSIONS
  Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Tansley
authors.forename: Zoe E
authors.initials: ZE
authors.lastname: Betteridge
authors.forename: Harsha
authors.initials: H
authors.lastname: Gunawardena
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Jacques
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Owens
authors.forename: Clarissa
authors.initials: C
authors.lastname: Pilkington
authors.forename: Katie
authors.initials: K
authors.lastname: Arnold
authors.forename: Shireena
authors.initials: S
authors.lastname: Yasin
authors.forename: Elena
authors.initials: E
authors.lastname: Moraitis
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: Neil J
authors.initials: NJ
authors.lastname: McHugh
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003882:Dermatomyositis / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D010641:Phenotype
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1