Anti-integrin αvβ6 autoantibodies are a novel predictive biomarker in ulcerative colitis

作者：Alexandra E. Livanos, Alexandra Dunn, Jeremy Fischer, Ryan C. Ungaro, Williams Turpin, Sun-Ho Lee, Shumin Rui, Diane Marie Del Valle, Julia Jougon, Gustavo Martínez-Delgado, Mark S. Riddle, Joseph A. Murray, Renée M. Laird, Joana Torres, Manasi Agrawal, Jared S Magee, Thierry Dervieux, Sacha Gnjatic, Dean Sheppard, Bruce E. Sands, Chad K. Porter, Kenneth Croitoru, Francesca Petralia, Jean‐Frédéric Colombel, Saurabh Mehandru · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2022 · DOI：10.1101/2022.11.21.517399 · 被引用次数：2 · 研究领域：Inflammatory Bowel Disease、Cell Adhesion Molecules Research、Systemic Lupus Erythematosus Research

Abstract Background and Aims Better biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvβ6 autoantibodies (anti-αvβ6) have been described in UC patients. Here, we tested for the presence of anti-αvβ6 antibodies in the pre-clinical phase of UC and studied their association with disease-related outcomes after diagnosis. Methods Anti-αvβ6 were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense pre-clinical cohort (PREDICTS). In a distinct, external validation cohort (GEM), we tested 12 pre-UC subjects and 49 matched controls. Further, anti-αvβ6 were measured in 2 incident UC cohorts (COMPASS n=55 and OSCCAR n=104) and associations between anti-αvβ6 and UC-related outcomes were defined using Cox proportional-hazards model. Results Anti-αvβ6 were significantly higher among individuals who developed UC compared to controls up to 10 years before diagnosis in PREDICTS. The anti-αvβ6 seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 timepoints. Anti-αvβ6 predicted UC development with an AUC of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvβ6 in pre-clinical UC samples was validated in the GEM cohort. Finally, high anti-αvβ6 was associated with a composite of adverse UC-outcomes including hos...