Association of Anti-CCAR1 Autoantibodies With Decreased Cancer Risk Relative to the General Population in Patients With Anti-Transcriptional Intermediary Factor 1-Positive Dermatomyositis

Objective. To describe the disease specificity, clinical phenotype, and risk of cancer in dermatomyositis (DM) patients with autoantibodies against cell division cycle and apoptosis regulator protein 1 (anti-CCAR1). Methods. The frequency of anti-CCAR1 autoantibodies was measured by enzyme-linked immunosorbent assay in the serum of DM patients from 2 independent cohorts (Johns Hopkins and Stanford), with patients with several other rheumatic diseases and healthy controls used as comparators. Clinical features and the risk of cancer incidence relative to that in the general population were determined in anti-CCAR1-positive DM patients. Results. Anti-CCAR1 antibodies were significantly associated with anti-transcriptional intermediary factor 1 gamma (antiTIF1 gamma) antibodies present in the serum of patients with DM: 80 (32%) of 252 anti-TIF1 gamma-positive DM patients versus 14 (8%) of 186 anti-TIF1 gamma-negativeDMpatients were positive for anti-CCAR1 antibodies (P < 0.001). Anti-CCAR1 antibodies were not detected in any of the 32 serum samples from healthy controls, and were present at very low frequencies in the sera of patients with other rheumatic diseases: 1 (2.3%) of 44 patients with anti-hydroxymethylglutaryl-coenzyme A reductasepositive necrotizingmyopathy, 1 (2.3%) of 44 patients with inclusion body myositis, and 3 (6.5%) of 46 patients with systemic lupus erythematosus were positive for anti-CCAR1 antibodies. Upon examining data on occurrence of cancer from the onset ofDMonward, the observed number of cancers diagnosed in anti-TIF-1 gamma-positiveDMpatients was significantly greater than expected in both cohorts, with a standardized incidence ratio (SIR) of 3.49 (95% confidence interval [95% CI] 2.39-4.92) in the Johns Hopkins cohort and a SIR of 4.54 (95% CI 3.04-6.52) in the Stanford cohort (each P < 0.001). DM patients who were both anti-TIF1 gamma positive and anti-CCAR1 positive had lower SIRs for cancer, with a SIR of 1.78 (95% CI 0.77-3.51) (P = 0.172) in the Johns Hopkins cohort and a SIR of 1.61 (95% CI 0.44-4.13) (P = 0.48) in the Stanford cohort. Conclusion. Anti-CCAR1 autoantibodies are specific for anti-TIF1.-positive DM. Their presence in anti-TIF1.positive patients attenuates the risk of cancer to a level comparable to that seen in the general population.