Anti-Integrin αvβ6 Autoantibodies Are a Novel Biomarker That Antedate Ulcerative Colitis

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 164; no. 4; pp. 619 - 629
• Main Authors: Livanos, Alexandra E., Dunn, Alexandra, Fischer, Jeremy, Ungaro, Ryan C., Turpin, Williams, Lee, Sun-Ho, Rui, Shumin, Del Valle, Diane Marie, Jougon, Julia J., Martinez-Delgado, Gustavo, Riddle, Mark S., Murray, Joseph A., Laird, Renee M., Torres, Joana, Agrawal, Manasi, Magee, Jared S., Dervieux, Thierry, Gnjatic, Sacha, Sheppard, Dean, Sands, Bruce E., Porter, Chad K., Croitoru, Kenneth, Petralia, Francesca, Abreu, Maria, Beck, Paul, Bernstein, Charles, Dieleman, Leo, Feagan, Brian, Griffiths, Anne, Guttman, David, Jacobson, Kevan, Kaplan, Gilaad, Krause, Denis O., Madsen, Karen, Marshall, John, Moayyedi, Paul, Ropeleski, Mark, Seidman, Ernest, Silverberg, Mark, Snapper, Scott, Stadnyk, Andy, Steinhart, Hillary, Surette, Michael, Turner, Dan, Walters, Thomas, Vallance, Bruce, Aumais, Guy, Bitton, Alain, Cino, Maria, Critch, Jeff, Denson, Lee, Deslandres, Colette, El-Matary, Wael, Herfarth, Hans, Higgins, Peter, Huynh, Hien, Hyams, Jeff, Mack, David, McGrath, Jerry, Otley, Anthony, Panancionne, Remo, Shapiro, Jason, Shah, Samir, Leleiko, Neal S., Colombel, Jean-Frederic, Mehandru, Saurabh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2023
• Subjects: Anti-Integrin αvβ6; Autoantibodies; Biomarkers; Colitis - complications; Colitis, Ulcerative - drug therapy; Crohn Disease - drug therapy; Humans; Inflammatory Bowel Disease; Medicin och hälsovetenskap; Proteomics; Ulcerative Colitis; COMPASS; CRP; CD; PREDICTS; Autoantibodies; OR; ESR; ROC; HR; IBD; OSCCAR; anti-αvβ6; UC; AUC; pANCA; Anti-Integrin αvβ6; ICD-9-CM; Ulcerative Colitis; Biomarkers; Inflammatory Bowel Disease; HC; CCC-GEM; ELISA
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2022.12.042

Better biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvβ6 (anti-αvβ6) autoantibodies have been described in patients with UC. We tested for the presence of anti-αvβ6 antibodies in the preclinical phase of UC and studied their association with disease-related outcomes after diagnosis. Anti-αvβ6 autoantibodies were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense preclinical cohort (PREDICTS [Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects]). In a distinct, external validation cohort (Crohn’s and Colitis Canada Genetic Environmental Microbial project cohort), we tested 12 pre-UC subjects and 49 matched controls. Furthermore, anti-αvβ6 autoantibodies were measured in 2 incident UC cohorts (COMPASS [Comprehensive Care for the Recently Diagnosed IBD Patients], n = 55 and OSCCAR [Ocean State Crohn's and Colitis Area Registry], n = 104) and associations between anti-αvβ6 autoantibodies and UC-related outcomes were defined using Cox proportional hazards model. Anti-αvβ6 autoantibodies were significantly higher among individuals who developed UC compared with controls up to 10 years before diagnosis in PREDICTS. The anti-αvβ6 autoantibody 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 time points. Anti-αvβ6 autoantibodies predicted UC development with an area under the curve of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvβ6 autoantibodies in preclinical UC samples was validated in the GEM cohort. Finally, high anti-αvβ6 autoantibodies 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. Anti-integrin αvβ6 autoantibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes. [Display omitted]