The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody

Rheumatology (Oxford). 2010 Mar;49(3):433-40. doi: 10.1093/rheumatology/kep375. Epub 2009 Dec 16.


Objectives: Various autoantibodies are detected in the sera of PM/DM patients. Some of them are specific to PM/DM patients and closely associated with clinical manifestations of the diseases. Recently, the anti-CADM-140 antibody was reported to be found specifically in clinically amyopathic DM (C-ADM) patients and to be associated with acute interstitial lung disease (ILD). We assessed the clinical significance of the anti-CADM-140 antibody and then investigated the autoantigen recognized by the anti-CADM-140 antibody.

Methods: Autoantibodies were screened in 192 patients with various CTDs and 21 healthy controls using immunoprecipitation with [(35)S]methionine-labelled HeLa cells. Immunoabsorbent column chromatography was used to purify an autoantigen that was subsequently subjected to peptide mass fingerprinting.

Results: The anti-CADM-140 antibody was revealed to be specific to DM. Most of the anti-CADM-140-positive patients were C-ADM although some of them showed apparent myositis. The anti-CADM-140-positive patients frequently showed hyperferritinaemia and acute progressive ILD with poor prognosis. The anti-CADM-140 antibody was shown to recognize IFN induced with helicase C domain protein 1 (IFIH1), also known as the melanoma differentiation-associated gene 5 (MDA5), which is one of the RIG-I-like receptors and plays a role in innate immune responses.

Conclusion: The anti-CADM-140 antibody was a marker of DM and intractable ILD and recognized IFIH1/MDA5, which is involved in innate immunity. These findings may give a new insight into the pathogenesis of DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Autoantibodies / immunology*
  • Autoantigens / blood*
  • Biomarkers / blood
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology*
  • Dermatomyositis / immunology*
  • HeLa Cells
  • Humans
  • Immunity, Innate
  • Intercellular Signaling Peptides and Proteins
  • Interferon-Induced Helicase, IFIH1
  • Molecular Sequence Data
  • Peptides / immunology*


  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • CADM-140 peptide, human
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1