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

Risa Nakanishi, Takeshi Kuwada, Masahiro Shiokawa, Yoshihiro Nishikawa, Sakiko Ota, Hajime Yamazaki, Takafumi Yanaidani, Kenji Sawada, Ayako Hirata, Muneji Yasuda, Ikuhisa Takimoto, Koki Chikugo, Masataka Yokode, Yuya Muramoto, Shimpei Matsumoto, Tomoaki Matsumoto, Norimitsu Uza, Tsutomu Chiba, Hiroshi Seno
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Abstract

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.
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抗整合素 αvβ6 抗体可预测溃疡性结肠炎患者在接受回肠肠袋-肛门吻合术的恢复性直肠切除术后出现的肠袋炎
背景溃疡性结肠炎(UC)患者最常见的并发症是带回肠袋-肛门吻合术(IPAA)的恢复性直肠结肠切除术(RPC)。我们曾报道过 UC 患者血清中存在抗整合素 αvβ6 抗体。本研究探讨了抗整合素αvβ6抗体与 UC 患者发生袋炎之间的关系。方法通过酶联免疫吸附试验检测了 16 名接受 RPC 和 IPAA 的 UC 患者血清中抗整合素αvβ6 抗体的水平。采用免疫组化和免疫印迹分析法检测了整合素αvβ6在结肠、回肠末端和肠袋上皮细胞中的表达。结果 UC 患者的抗整合素 αvβ6 抗体水平在 RPC 后 3 个月、9 个月和 12 个月显著下降(P < 0.05)。然而,在发生胃袋炎的患者中,抗体水平仍然很高。与未发生胃袋炎的患者相比,发生 RPC 时的抗体水平明显更高。Kaplan-Meier 分析显示,在 RPC 时抗体水平高于临界值的患者中,储袋炎的发生率明显更高。结论 RPC 后 UC 患者体内的抗整合素 αvβ6 抗体水平下降,但发生储袋炎的患者体内的抗整合素 αvβ6 抗体水平仍然很高。RPC 时的抗体水平可作为预测 UC 患者罹患储袋炎风险的潜在预后生物标志物。
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