RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

Arthritis Rheum. 2009 Jul;60(7):2193-200. doi: 10.1002/art.24621.


Objective: To identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C-ADM) and rapidly progressive interstitial lung disease (ILD).

Methods: An anti-CADM-140 antibody-positive prototype serum sample was used to screen a HeLa cell-derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro-transcribed and in vitro-translated products using anti-CADM-140 antibody-positive and anti-CADM-140 antibody-negative sera. The lysates of COS-7 cells transfected with the putative antigen were similarly tested. An enzyme-linked immunosorbent assay (ELISA) to detect the anti-CADM-140 antibody was established using a recombinant CADM-140 antigen, and its specificity and sensitivity for C-ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases.

Results: By cDNA library screening and immunoprecipitation of in vitro-transcribed and in vitro-translated products, we obtained a cDNA clone encoding melanoma differentiation-associated gene 5 (MDA-5). The anti-CADM-140 antibodies in patients' sera specifically reacted with MDA-5 protein expressed in cells transfected with full-length MDA-5 cDNA, confirming the identity of MDA-5 as the CADM-140 autoantigen. The ELISA, using recombinant MDA-5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the "gold standard" immunoprecipitation assay, and was useful for identifying patients with C-ADM and/or rapidly progressive ILD.

Conclusion: Given that RNA helicase encoded by MDA-5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C-ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA-5 protein makes detection of the anti-CADM-140 antibody routinely available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / blood
  • Antibodies, Anti-Idiotypic / immunology
  • Autoantigens / blood
  • Autoantigens / immunology*
  • COS Cells
  • Case-Control Studies
  • Chlorocebus aethiops
  • DEAD-box RNA Helicases / blood
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology*
  • DNA, Complementary / blood
  • DNA, Complementary / genetics
  • Dermatomyositis / blood
  • Dermatomyositis / immunology*
  • Disease Progression
  • Humans
  • Interferon-Induced Helicase, IFIH1
  • Lung Diseases, Interstitial / blood
  • Lung Diseases, Interstitial / immunology*
  • RNA Helicases / blood
  • RNA Helicases / genetics
  • RNA Helicases / immunology*
  • Sensitivity and Specificity
  • Transfection


  • Antibodies, Anti-Idiotypic
  • Autoantigens
  • DNA, Complementary
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • RNA Helicases