The Relationship Between Anti–Cell Division Cycle and Apoptosis Regulator 1 Autoantibodies, Anti‐Sp4 Autoantibodies, and Cancer in Anti–Transcription Intermediary Factor 1γ–Positive Dermatomyositis

ObjectiveThe objective of this study was to describe the frequency, co‐occurrence, and cancer association of anti–cell division cycle and apoptosis regulator 1 (anti‐CCAR1) and anti‐Sp4 in two large independent adult dermatomyositis (DM) cohorts.MethodsAnti–transcription intermediary factor 1γ (anti‐TIF1γ)–positive patients with DM from two independent cohorts were studied to determine the serologic overlap of anti‐CCAR1 and anti‐Sp4 autoantibodies measured by enzyme‐linked immunosorbent assay. Associations between cancer‐associated myositis (CAM) and antibody‐defined subgroups within anti‐TIF1γ–positive patients with DM were determined.ResultsA total of 305 anti‐TIF1γ–positive patients with DM were studied: 169 patients from Johns Hopkins and 136 patients from Stanford. In each cohort, approximately one‐third of anti‐TIF1γ–positive patients with DM were anti‐Sp4 positive, one‐third were anti‐CCAR1 positive, 20% were positive for both, and half of patients were negative for both. There was a strong association with CAM in patients lacking both these antibodies (Johns Hopkins, odds ratio [OR] 12.9 [95% confidence interval (CI) 3.6–89.5]; Stanford, OR 4.5 [95% CI 1.8–13.2]). The strongest negative association with CAM was found in patients with anti‐Sp4 or anti‐CCAR1 (Johns Hopkins, OR 0.07 [95% CI 0.01–0.27]; Stanford, OR 0.22 [95% CI 0.07–0.55]).ConclusionBoth anti‐Sp4 and anti‐CCAR1 autoantibody subgroups are negatively associated with CAM. Although the magnitude of this association is substantial, cancer occasionally occurs in patients positive for either specificity. Conversely, approximately half of anti‐TIF1γ–positive patients with DM are negative for both antibodies (anti‐Sp4/anti‐CCAR1 negative), and thus this subgroup may warrant more intensive cancer surveillance.