Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

BACKGROUND AND AIMS: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. METHODS: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. RESULTS: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin alpha v beta 6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti-integrin alpha v beta 6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti-integrin alpha v beta 6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin alpha v beta 6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin alpha v beta 6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. CONCLUSIONS: A significant majority of patients with ulcerative colitis had autoantibodies against integrin alpha v beta 6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity.