Gastroenterology Unit, Fondazione Policlinico Universitario Campus Bio-Medico and Università Campus Bio-Medico di Roma, 00128 Rome, Italy.
Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), International Campus "A. Buzzati-Traverso", Via E. Ramarini 32, Monterotondo Scalo, 00015 Rome, Italy.
Int J Mol Sci. 2024 May 27;25(11):5817. doi: 10.3390/ijms25115817.
Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm vs. HV 20.70 ± 1.52 Ω × cm, < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm, < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn's disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm predicted response to VDZ (OR 11; CI 2-59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy.
维得利珠单抗（VDZ）用于治疗炎症性肠病（IBD）患者。目前缺乏研究 VDZ 治疗后结肠上皮屏障功能的体外研究。本研究旨在评估 IBD 患者在基线时和 VDZ 治疗 24 周和 52 周时的结肠上皮屏障功能，并探讨屏障功能与临床参数之间的关系。从 23 例 IBD 患者（治疗前，治疗后 24 周和 52 周）和 26 例健康志愿者（HV）中获得结肠标本。在 Ussing 室中测量跨上皮电阻（TEER，离子通透性）和细胞旁通透性。IBD 患者的离子跨上皮通透性增加（TEER，13.80 ± 1.04 Ω × cm 比 HV 20.70 ± 1.52 Ω × cm， < 0.001），而 4 kDa 探针的细胞旁通透性没有变化。经过 52 周的治疗，VDZ 增加了 TEER（18.09 ± 1.44 Ω × cm， < 0.001）。24 周时，58%和 25%的溃疡性结肠炎患者以及 52 周时 62%和 50%的克罗恩病患者出现临床应答。临床和内镜评分与 TEER 密切相关。TEER < 14.65 Ω × cm 预测对 VDZ 的反应（OR 11；CI 2-59）。VDZ 降低了治疗前 IBD 患者结肠上皮中观察到的离子通透性增加，与临床、组织学（炎症浸润）和内镜改善平行。低 TEER 预测对 VDZ 治疗的临床反应。
