Anti-MDA5 and anti-TIF1-gamma antibodies have clinical significance for patients with dermatomyositis.
OBJECTIVE
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.
Hoshino
Kei
K
Department of Dermatology, Division of Connective Tissue Disease and Autoimmunity, Nagoya University Graduate School of Medicine, 65 Turumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Muro
Yoshinao
Y
Sugiura
Kazumitsu
K
Tomita
Yasushi
Y
Nakashima
Ran
R
Mimori
Tsuneyo
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003882:Dermatomyositis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D017563:Lung Diseases, Interstitial / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000150:complications; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D009687:Nuclear Proteins / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D015415:Biomarkers; D009687:Nuclear Proteins; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1