Clinical Features and Immunogenetic Risk Factors Associated With Additional Autoantibodies in Anti-Transcriptional Intermediary Factor 1γ Juvenile-Onset Dermatomyositis

Objective: Novel autoantibody specificities including anti-CCAR1 were recently discovered in adult patients with anti-transcriptional intermediary factor (TIF1)–positive dermatomyositis (DM) and were associated with attenuated cancer emergence. The aims of the present study were to examine whether these autoantibodies occur in patients with juvenile-onset DM (JDM) and to determine their associated features. Methods: Sera from 150 patients with anti-TIF1γ autoantibody-positive JDM in a cross-sectional cohort and 90 juvenile healthy controls were assayed for anti-CCAR1, anti-C1Z1, anti-IMMT, anti-TBL1XR1, and anti-Sp4 autoantibodies. Demographics, myositis autoantibodies, clinical features, medications, outcomes, and HLA-DRB1 and HLA-DQA1 alleles were compared between those with and without these autoantibodies. Results: Any one of the anti-TIF1γ-associated autoantibodies was present in 44 patients (29%) overall, including 25 (17%) with anti-Sp4, 22 (15%) with anti-TBL1XR1, 14 (9%) with anti-CCAR1, 2 (1%) with anti-C1Z1, and 2 (1%) with anti-IMMT autoantibodies. These anti-TIF1γ-associated autoantibodies frequently co-occurred. Patients with any of the anti-TIF1γ-associated autoantibodies had less frequent falling (34% [15] vs. 53% [56], P = 0.032) and lower peak muscle enzymes. None of the patients had cancer. Among White patients, HLA-DRB1*03 was protective against an anti-TIF1γ-associated autoantibody (odds ratio 0.20, 95% confidence interval 0.07–0.52). Conclusion: Autoantibodies associated with anti-TIF1γ were found in isolation and in combination among a subset of patients with JDM. Patients with these autoantibodies had less severe muscle disease and were not enriched for HLA-DRB1*03. Additional autoantibodies among patients with positive anti-TIF1γ with JDM likely contribute to the heterogeneity of the anti-TIF1γ serologic subgroup.