Department of Gastroenterology of the Hospital Universitario de Fuenlabrada, Madrid, Spain.
J Crohns Colitis. 2013 Dec;7(11):e569-79. doi: 10.1016/j.crohns.2013.04.005. Epub 2013 May 1.
Angiogenic and lymphangiogenic factors (ALFs) may play an important role in inflammatory bowel disease (IBD). Our aims were to evaluate levels of ALFs in serum and the colonic mucosa culture supernatant (MCS) of patients with active and quiescent IBD and healthy subjects and to correlate them with the endoscopic, clinical and histological activity and with acute-phase reactants.
This is a prospective study of 28 controls and 72 IBD patients. Serum and MCS concentration of VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, PlGF, Ang1, Ang2 and Tie2 were measured by ELISA. Activity was established by specific indexes (CDAI, Mayo score, SES-CD, D'Haens scale and Riley index). Acute-phase reactants were routinely measured.
MCS levels of all ALFs except VEGFR3 were higher in patients with endoscopic (p<0.05), clinical (p<0.05) and histological (p<0.01) activity than in those without it. In serum, VEGFA, VEGFC and Ang1 and VEGFA and Ang1 levels were lower in patients in remission than in patients with clinical and histological activity, respectively (p<0.05). There was a correlation between serum and MCS concentrations for VEGFD, VEGFR3, PlGF and Tie2 (r=0.25, r=0.48, r=-0.45 and r=0.36; p<0.05). Ang2 in MCS was the best predictor for the diagnosis of endoscopic, histological and clinical activity (area under ROC curve>0.8).
MCS determination suggests a local increase in ALFs that correlates with IBD activity. Although the correlation between ALFs in serum and MCS was not good, the study of some of these factors as possible targets of new drugs for IBD constitutes a key new line of research.
血管生成和淋巴管生成因子(ALFs)可能在炎症性肠病(IBD)中发挥重要作用。我们的目的是评估活动期和缓解期 IBD 患者及健康对照者血清和结肠黏膜培养上清液(MCS)中 ALFs 的水平,并将其与内镜、临床和组织学活动及急性期反应物相关联。
这是一项前瞻性研究,纳入 28 名对照者和 72 名 IBD 患者。采用 ELISA 法测定血清和 MCS 中 VEGFA、VEGFC、VEGFD、VEGFR1、VEGFR2、VEGFR3、PlGF、Ang1、Ang2 和 Tie2 的浓度。通过特定指标(CDAI、Mayo 评分、SES-CD、D'Haens 评分和 Riley 指数)评估活动度。常规检测急性期反应物。
与无内镜(p<0.05)、临床(p<0.05)和组织学(p<0.01)活动的患者相比,有内镜、临床和组织学活动的患者的 MCS 中所有 ALFs 的水平均较高(p<0.05)。在血清中,缓解期患者的 VEGFA、VEGFC 和 Ang1 及 VEGFA 和 Ang1 水平分别低于有临床和组织学活动的患者(p<0.05)。血清和 MCS 中 VEGFD、VEGFR3、PlGF 和 Tie2 之间存在相关性(r=0.25、r=0.48、r=-0.45 和 r=0.36;p<0.05)。MCS 中的 Ang2 是内镜、组织学和临床活动诊断的最佳预测因子(ROC 曲线下面积>0.8)。
MCS 测定提示 ALFs 局部增加,与 IBD 活动相关。尽管血清和 MCS 中 ALFs 之间的相关性不佳,但研究其中一些因子作为 IBD 新药的可能靶点构成了一个关键的新研究方向。