title: Prevalence and clinical significance of anti-MDA5 antibodies in European patients with polymyositis/dermatomyositis.
abstract: OBJECTIVE
  Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease characterised by skin and muscle inflammation, internal organ involvement and serum disease-specific autoantibodies. The recently identified anti-MDA5 (melanoma differentiation-associated gene 5) antibodies are associated with clinically amyopathic DM (CADM), rapidly progressive interstitial lung disease, severe skin manifestations, and poor prognosis. Our objective was to examine the clinical significance of anti-MDA5 antibodies in a cohort of European Caucasian patients with PM/DM, considering that data on anti-MDA5 serology are limited to Asian and US cohorts.
  
  
  METHODS
  Sera from 76 consecutive adult Italian patients with PM/DM were analysed by immunoprecipitation (IP) of 35S-methionine radiolabelled HeLa and K562 cell extracts, ELISA using recombinant MDA5 protein and IP-Western Blot using rabbit anti-MDA5 antibodies. Clinical associations of anti-MDA5 antibody positive patients were analysed.
  
  
  RESULTS
  Anti-MDA5 antibodies were identified in 5/76 (7%) PM/DM cases and all 5 cases were CADM; anti-MDA5 was the second most common autoantibody in DM after anti-MJ/NXP-2, found in 24% of cases. Compared to 29 anti-MDA5 (-) DM, anti-MDA5 (+) patients have more typical DM skin disease (digit pulp/periungual lesions, Gottron's papules, heliotrope rash) (p=ns). Interstitial lung disease was observed in 3/5 anti-MDA5 (+) patients but only 14% of anti-MDA5 (-) cases (p=0.048).
  
  
  CONCLUSIONS
  Our study on European patients with PM/DM confirms that anti-MDA5 antibodies are not uncommon. All anti-MDA5 (+) cases are affected by CADM with typical skin disease, while rapidly progressive pulmonary involvement was diagnosed only in one case. Further studies in larger cohorts are necessary to define the clinical significance of anti-MDA5 antibodies in European PM/DM.
authors.affiliation: Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Rozzano (Milan), and BIOMETRA Department, University of Milan, Milan, Italy. dott.ceribelli@libero.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Ceribelli
authors.forename: Micaela
authors.initials: M
authors.lastname: Fredi
authors.forename: Mara
authors.initials: M
authors.lastname: Taraborelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cavazzana
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.forename: Jason Y F
authors.initials: JY
authors.lastname: Chan
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Franco
authors.initials: F
authors.lastname: Franceschini
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003882:Dermatomyositis / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D000072640:Interferon-Induced Helicase, IFIH1; D007558:Italy / Q000453:epidemiology; D020014:K562 Cells; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D015995:Prevalence; D012189:Retrospective Studies; D044465:White People
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1