Anti-integrin αvβ6 antibodies predict pouchitis in patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis

Background Pouchitis is the most common complication of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We previously reported the presence of anti-integrin αvβ6 antibodies in the serum of patients with UC. This study investigated the association between anti-integrin αvβ6 antibodies and the development of pouchitis in patients with UC. Methods Serum levels of anti-integrin αvβ6 antibodies were measured by enzyme-linked immunosorbent assay in 16 patients with UC who underwent RPC with IPAA. Integrin αvβ6 expression in the colonic, terminal ileal, and pouch epithelium was examined using immunohistochemistry and western blot analysis. Results Anti-integrin αvβ6 antibody levels in patients with UC were significantly decreased at 3, 9, and 12 months after RPC (P < 0.05). However, in patients who developed pouchitis, antibody levels remained high. The antibody levels at the time of RPC were significantly higher in patients who developed pouchitis compared to those who did not. Kaplan-Meier analysis revealed a significantly higher incidence of pouchitis in patients with antibody levels above the cutoff at the time of RPC. Although integrin αvβ6 was not expressed in the terminal ileal epithelium at the time of RPC, expression became positive in the pouch epithelium of patients with pouchitis. Conclusions The anti-integrin αvβ6 antibody levels in patients with UC were decreased after RPC, but remained high in patients who developed pouchitis. The antibody levels at the time of RPC may serve as a potential prognostic biomarker for predicting the risk of pouchitis in patients with UC. ### Competing Interest Statement Takeshi Kuwada, Masahiro Shiokawa, Tsutomu Chiba, and Hiroshi Seno licensed a patent to Medical and Biological Laboratories Co., Ltd. ### Funding Statement the Japan Society for the Promotion of Science (Grant-in-Aid for Early-Career Scientists 22K16017 to Takeshi Kuwada). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Kyoto University Hospital gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript