Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies

Abstract

ObjectivesIn dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies.MethodsPhage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren’s syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies.ResultsAnti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer.ConclusionsAnti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.

Autoantibodies Recognizing Specificity Protein 4 Co‐occur With Anti–Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis

“…Several features are similar in adult and pediatric populations of anti‐Sp4 autoantibody–positive patients with myositis (7). In both populations, anti‐Sp4 autoantibodies are highly associated with anti‐TIF1 autoantibodies.…”

Current concepts and advances in dermatomyositis: a dermatological perspective

“…frequently targeted antigen associated with cancer protection (63). Hosono et al have recently reported a similar cancer-protective association with anti-Sp4 autoantibodies (64).…”

A Combination of Autoantibodies Predicts the Fate of Cancer‐Associated Dermatomyositis

“…It is intriguing that autoantibodies against a transcription factor, specificity protein 4 (Sp4), as recently reported in a study by Hosono et al (7), display features similar to those of anti-CCAR1 autoantibodies. Anti-Sp4 autoantibodies were demonstrated to be specific for DM: they were present in 10.5% of patients with DM but were rarely found in healthy individuals or patients with other rheumatic diseases.…”

“…Anti‐Sp4 autoantibodies were demonstrated to be specific for DM: they were present in 10.5% of patients with DM but were rarely found in healthy individuals or patients with other rheumatic diseases. Moreover, among patients with DM, anti‐Sp4 autoantibodies were found almost exclusively in those with coexisting anti‐TIF1γ autoantibodies (7). Similar to the current study by Fiorentino et al (5), the prevalence of cancer was relatively decreased in those with coexisting anti‐Sp4 autoantibodies and anti‐TIF1γ autoantibodies.…”