Anti-integrin αvβ6 autoantibodies are a novel biomarker that antedate ulcerative colitis
抗整合素αvβ6自身抗体可作为先于溃疡性结肠炎的新型生物标志物
10.1053/j.gastro.2022.12.042
01-09, Article
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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 hospitalization, disease extension, colectomy, systemic steroid use and/or escalation to biologic therapy in recently diagnosed UC.
Conclusion: Anti-integrin αvβ6 auto-antibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.
First Authors:
Alexandra E Livanos
Correspondence Authors:
Jean Frederic Colombel,Saurabh Mehandru
All Authors:
Alexandra E Livanos,Alexandra Dunn,Jeremy Fischer,Ryan C Ungaro,Williams Turpin,Sun-Ho Lee,Shumin Rui,Diane Marie Del Valle,Julia J Jougon,Gustavo Martinez-Delgado,Mark S Riddle,Joseph A Murray,Renee 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,CCC-GEM Project Research Consortium,OSCCAR Consortium,Jean Frederic Colombel,Saurabh Mehandru
