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

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-g (TIF1-g) were identified in DM. Here, we detected these autoantibodies in patient sera using new assays with recombinant MDA5 and TIF1-g, and associated clinical features with the presence of anti-MDA5 or anti-TIF1-g 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-g 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-g, and anti-TIF1-g antibodies were only detected in DM patients. Strikingly, 7 (58%) of 12 patients with cancer-associated DM had sera that reacted with TIF1-g. Anti-TIF1-g-positive DM patients had significantly more internal malignancies than anti-TIF1-g-negative DM patients (58 vs 9%, P < 0.001). Conclusions. Anti-MDA5 and anti-TIF1-g antibodies were confirmed to be serological DM subset markers. Anti-MDA5 and anti-TIF1-g antibodies were detected based on their ability to immunoprecipitate biotinylated recombinant MDA5 and TIF1-g, and were closely associated with life-threatening complications in DM.