*Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA.
Center for Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco (UCSF), San Francisco, California, USA.
Inflamm Bowel Dis. 2022 Aug 1;28(8):1219-1228. doi: 10.1093/ibd/izac056.
Anti-α4β7 (Vedolizumab) treats inflammatory bowel disease (IBD) by blocking the interaction between integrin α4β7 on leukocytes and mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) on the gut endothelium. Women with IBD often require continuing biologic therapy during pregnancy to avoid disease flare. To date, there have been no reports of an increase in adverse events with Vedolizumab use during pregnancy. Notably, integrins play a major role in human placental development during pregnancy. It is unknown whether Vedolizumab disrupts placental cell (cytotrophoblast) invasion and/or adhesion by blocking interactions with MAdCAM-1. We therefore investigated human placental expression of MAdCAM-1, the role of MAdCAM-1/α4β7 interactions in cytotrophoblast invasion/adhesion in vitro, and whether Vedolizumab administration in vivo alters the placental structure.
Histological sections of placentas from normal pregnancies were evaluated for MAdCAM-1 expression by immunofluorescence. The impacts of Vedolizumab or anti-integrin β7 on human cytotrophoblast invasion and adhesion were assessed. Histology results from term placentas of 2 patients with IBD receiving Vedolizumab were compared to those of untreated healthy controls.
Placental MAdCAM-1 expression was predominantly associated with invading extravillous cytotrophoblasts at the maternal-fetal interface. Treatment of isolated primary cytotrophoblasts with Vedolizumab or anti-integrin β7 significantly reduced Matrigel invasion, adherence to a MAdCAM-1-coated substrate, and interactions with HuT-78 cells. Placentas from 2 Vedolizumab-treated patients with IBD exhibited pronounced pathologic features as compared to healthy control specimens.
This study revealed a previously unrecognized role for α4β7 and MAdCAM-1 in human placentation. More clinical and histological data from Vedolizumab-treated pregnant patients will be necessary to determine whether this medication poses any risk to the mother and fetus.
抗-α4β7（Vedolizumab）通过阻断白细胞整合素 α4β7 与肠道内皮细胞上的粘膜地址素细胞黏附分子-1（MAdCAM-1）之间的相互作用来治疗炎症性肠病（IBD）。患有 IBD 的女性在怀孕期间通常需要继续接受生物治疗以避免疾病发作。迄今为止，尚无关于 Vedolizumab 在怀孕期间使用会增加不良事件的报道。值得注意的是，整合素在怀孕期间对人类胎盘发育起着重要作用。目前尚不清楚 Vedolizumab 是否通过阻断与 MAdCAM-1 的相互作用来破坏胎盘细胞（滋养细胞）的侵袭和/或黏附。因此，我们研究了 MAdCAM-1 在人胎盘中的表达，MAdCAM-1/α4β7 相互作用在体外滋养细胞侵袭/黏附中的作用，以及体内给予 Vedolizumab 是否改变胎盘结构。
通过免疫荧光法评估正常妊娠胎盘组织切片中 MAdCAM-1 的表达。评估 Vedolizumab 或抗整合素β7 对人滋养细胞侵袭和黏附的影响。比较 2 例接受 Vedolizumab 治疗的 IBD 患者的足月胎盘组织的组织学结果与未经治疗的健康对照组。
胎盘 MAdCAM-1 的表达主要与母胎界面的侵袭性绒毛外滋养细胞有关。用 Vedolizumab 或抗整合素β7 处理分离的原代滋养细胞可显著减少 Matrigel 侵袭、黏附在 MAdCAM-1 包被的基质上以及与 HuT-78 细胞的相互作用。与健康对照组标本相比，来自 2 例接受 Vedolizumab 治疗的 IBD 患者的胎盘表现出明显的病理性特征。
本研究揭示了 α4β7 和 MAdCAM-1 在人类胎盘形成中的先前未被认识的作用。需要更多来自接受 Vedolizumab 治疗的妊娠患者的临床和组织学数据，以确定该药物是否对母亲和胎儿有任何风险。
