Anti-MDA5 and anti-TIF1-gamma antibodies have clinical significance for patients with dermatomyositis

Rheumatology (Oxford). 2010 Sep;49(9):1726-33. doi: 10.1093/rheumatology/keq153. Epub 2010 May 25.

Abstract

Objectives: Myositis-specific autoantibodies are useful for diagnosing PM/DM. Recently, two new myositis-specific autoantibodies against melanoma differentiation-associated gene 5 (MDA5) and transcriptional intermediary factor 1-gamma (TIF1-gamma) were identified in DM. Here, we detected these autoantibodies in patient sera using new assays with recombinant MDA5 and TIF1-gamma, and associated clinical features with the presence of anti-MDA5 or anti-TIF1-gamma antibodies.

Methods: We screened 135 Japanese patients with various CTDs, including 82 with DM. DM patients were classified as clinically amyopathic DM (CADM), cancer-associated DM or classical DM without cancer. Anti-MDA5 and anti-TIF1-gamma antibodies were detected by their ability to immunoprecipitate biotinylated recombinant proteins.

Results: Sera from 21 (26%) of 82 DM patients immunoprecipitated MDA5, and every anti-MDA5-positive patient had DM (except one patient with SSc). Sera from 20 (65%) of 31 CADM patients reacted with MDA5. Notably, anti-MDA5-positive DM patients had significantly more interstitial lung disease than anti-MDA5-negative DM patients (95 vs 32%, P < 0.001). Sera from 12 (15%) of 82 DM patients immunoprecipitated TIF1-gamma, and anti-TIF1-gamma antibodies were only detected in DM patients. Strikingly, 7 (58%) of 12 patients with cancer-associated DM had sera that reacted with TIF1-gamma. Anti-TIF1-gamma-positive DM patients had significantly more internal malignancies than anti-TIF1-gamma-negative DM patients (58 vs 9%, P < 0.001).

Conclusions: Anti-MDA5 and anti-TIF1-gamma antibodies were confirmed to be serological DM subset markers. Anti-MDA5 and anti-TIF1-gamma antibodies were detected based on their ability to immunoprecipitate biotinylated recombinant MDA5 and TIF1-gamma, and were closely associated with life-threatening complications in DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian People
  • Autoantibodies / immunology*
  • Biomarkers
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • DEAD-box RNA Helicases / immunology*
  • Dermatomyositis / complications*
  • Dermatomyositis / immunology
  • Dermatomyositis / pathology
  • Female
  • Humans
  • Interferon-Induced Helicase, IFIH1
  • Lung Diseases, Interstitial / etiology*
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / pathology
  • Male
  • Melanoma / complications
  • Middle Aged
  • Neoplasms / complications
  • Nuclear Proteins / immunology*
  • Transcription Factors / immunology*
  • Young Adult

Substances

  • Autoantibodies
  • Biomarkers
  • Nuclear Proteins
  • Transcription Factors
  • transcriptional intermediary factor 1
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1