Background: Although pouchitis is a common complication in patients with ulcerative colitis (UC) who underwent a proctocolectomy with ileal pouch-anal anastomosis (IPAA), the etiology of pouchitis remains unknown. Recent studies have identified a novel autoantibody against integrin αvβ6 in the serum of UC patients, which is correlated with disease activity. This antibody can become not only diagnostic biomarker but preclinical biomarker, implicating that this autoantibody might play a central role in the pathogenesis of UC. We herein assessed the association between concentrations of serum anti-integrin αvβ6 antibody and pouch inflammation in patients with postoperative UC.
Methods: The concentrations of anti-integrin αvβ6 antibodies were measured with enzyme-linked immunosorbent assay on sera from UC patients post proctocolectomy with IPAA and controls. Clinical and endoscopic activities of pouchitis were assessed using modified Pouchitis Disease Activity Index (mPDAI). Pouchitis was defined as mPDAI of ≥ 5.
Results: We examined the sera from a total 38 subjects, which consisted of 28 patients who underwent IPAA, 5 healthy controls and 5 patients with moderate-to-severe UC. Median age of the patients who underwent IPAA was 51.50 [IQR, 45.00-54.75] years old, 60.7 % of those were male. The median values of anti-integrin αvβ6 (U/mL) in postoperative patients with UC were significantly higher than healthy control (758 [IQR, 354-1679] vs. 43 [IQR, 11-62], P = 0.001) and significantly lower than patients with moderate-to-severe UC (758 [IQR, 354-1679] vs. 3491 [IQR, 3438-4907], P = 0.018). In the postoperative UC patients with IPAA, 12 of 28 patients (43%) had pouchitis. The median values of anti-integrin αvβ6 antibodies were significantly higher in patients with pouchitis than those without pouchitis (1431 [IQR, 393-3304] vs. 520 [IQR, 156-996], P = 0.047) (Figure A). Receiver operating characteristic curve was constructed to assess the accuracy of anti-integrin αvβ6 antibodies for diagnosis of pouchitis (Figure B). The area under the curve for anti-integrin αvβ6 antibodies was 0.724 (95% CI, 0.524-0.924). There was no significant correlation between mPDAI and anti-integrin αvβ6 antibodies, but mPDAI endoscopic subscore was correlated with the values of anti-integrin αvβ6 antibodies (r = 0.48, P = 0.011).
Conclusions: The concentration of anti-integrin αvβ6 antibodies are increased significantly in patients with pouchitis. The results suggest that αvβ6 antibody can be not only a potential new biomarker for the diagnosis and activity of pouchitis, but also a possible link to the pathogenesis of pouchitis in postoperative UC patients.

Figure A

Figure B

Koji Otani

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