RT Journal Article
SR Electronic
T1 Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP annrheumdis-2022-222441
DO 10.1136/ard-2022-222441
A1 Yuji Hosono
A1 Brandon Sie
A1 Iago Pinal-Fernandez
A1 Katherine Pak
A1 Christopher A Mecoli
A1 Maria Casal-Dominguez
A1 Blake M Warner
A1 Mariana J Kaplan
A1 Jemima Albayda
A1 Sonye Danoff
A1 Thomas E Lloyd
A1 Julie J Paik
A1 Eleni Tiniakou
A1 Rohit Aggarwal
A1 Chester V Oddis
A1 Siamak Moghadam-Kia
A1 Carmelo Carmona-Rivera
A1 Jose César Milisenda
A1 Josep Maria Grau-Junyent
A1 Albert Selva-O'Callaghan
A1 Lisa Christopher-Stine
A1 H Benjamin Larman
A1 Andrew Lee Mammen
YR 2022
UL http://ard.bmj.com/content/early/2022/08/25/ard-2022-222441.abstract
AB Objectives In 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.Methods Phage 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.Results Anti-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.Conclusions Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.Data are available upon reasonable request. All data relevant to the study are either included in the article or will be shared upon request.