Antibodies against Integrin αvβ6 have high diagnostic accuracy for ulcerative colitis

Patrick Bez¹Martina Scapolan²Davide Giuseppe Ribaldone³Gian Paolo Caviglia³Silvia Zago²Cristina Trucco³Simone Frara³Antonino Caruso⁴Marta Ascolani⁴Michele Campigotto⁴Stefano Benvenuti⁴Stefano Martelossi⁵Lara De Lucchi¹Marta Favero¹Francesco Cinetto^1,6Elisabetta Faggin⁶Marcello Rattazzi^1,6Laura Ventura⁷Tilde Manetta⁸Giulio Mengozzi³Antonio Antico²Carla Felice^9*

• ¹Medicine 1, Ca' Foncello University Hospital, Treviso, Italy
• ²Department of Laboratory Medicine, Ca’ Foncello University Hospital, Treviso, Italy
• ³Department of Medical Sciences, University of Turin, Turin, Italy
• ⁴Gastroenterology Unit, Ca' Foncello University Hospital, Treviso, Italy
• ⁵Pediatric Unit, Ca' Foncello University Hospital, Treviso, Italy
• ⁶Department of Medicine (DIMED), Universita degli Studi di Padova, Padua, Italy
• ⁷Department of Statistical Sciences, Universita degli Studi di Padova, Padua, Italy
• ⁸Department of Laboratory Medicine, Città della Salute e della Scienza - Molinette Hospital, Turin, Italy
• ⁹Department of Medicine (DIMED), University of Padua, Padua, Italy

Background: Anti-Integrin αvβ6 IgG autoantibodies showed good sensitivity and optimal specificity in ulcerative colitis compared to controls. We aim at confiming the diagnostic accuracy of anti-Integrin αvβ6 autoantibodies in an Italian multicentric cohort. Methods: This observational multicentric study included adult and pediatric patients with inflammatory bowel disease and controls. Demographics, disease extension, partial Mayo Score (PMS), fecal calprotectin, endoscopic Mayo score, and the time to the composite outcome including hospitalization or colectomy were collected. A new commercial ELISA kit was used to measure anti-Integrin αvβ6 in the serum of enrolled patients. Receiver operating curve (ROC) was used to identify the optimal cut-off to discriminate UC from other patients. Kaplan-Meier curves and log-rank test were used to analyze the composite outcome. Results: A total of 228 patients were enrolled, including 36 controls (13 healthy donors and 24 diseased controls), 34 irritable bowel syndrome (IBS), 50 CD, and 107 UC. UC patients presented higher values of anti-Integrin αvβ6 IgG compared to CD, IBS, and controls (Kruskal Wallis test and post-hoc Holm's correction: p<0.001). The ROC of anti-Integrin αvβ6 IgG performed optimally with an area under the curve (AUC) of 0.93. The optimal cut-off to distinguish UC from controls was 1.68 U/ml with a sensitivity of 87.9% and a specificity of 86.8% compared to non-UC patients with a specificity of 94.4% to non-IBD and 76% to CD, with very similar values to a recent multicentric study. A higher threshold up to 13 U/ml may be useful to make a differential diagnosis between UC and CD with a specificity of 90%. Anti-Integrin αvβ6 did not correlate with clinical disease activity, but weakly with FCP (R=0.28, p=0.36) and moderately with endoscopic disease activity reported at the last colonoscopy (R=0.60, p=0.03). Despite the low number of events, the log-rank test showed the potential predictive performance of high levels of anti-integrin αvβ6 IgG (i.e. >17 U/ml) for the composite outcome (p=0.02). Conclusions: This study validates a new anti-Integrin αvβ6 ELISA kit and confirms its high diagnostic accuracy in UC also in an European population, with particular utility in the differential diagnosis of specific forms of IBD.