Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA.
Prometheus Laboratories, San Diego, California, USA.
Gut. 2016 Feb;65(2):249-55. doi: 10.1136/gutjnl-2014-308099. Epub 2015 Feb 10.
The aim of this study was to assess the correlation between serum and intestinal anti-tumour necrosis factor (TNF) levels, and their relationship to endoscopic disease activity and levels of TNF.
Cross-sectional study of 30 patients receiving treatment with infliximab or adalimumab for Crohn's disease or UC. For each patient, a sample of serum was matched to tissue biopsies. Endoscopic and histological disease activity was recorded for each tissue sample.
There was a significant positive correlation between anti-TNF in serum and tissue (r=0.3920, p=0.002), especially in uninflamed tissue (r=0.50, p<0.001), but not with those samples that had inflammation (r=0.19, p=0.54). Anti-TNF concentration in tissue correlated with degree of endoscopic inflammation, except for tissue with severe inflammation in which anti-TNF levels were again lower (mean normalised anti-TNF in tissue: uninflamed=0.93, mild=2.17, moderate=13.71, severe=2.2 inflammation (p=0.0042)). The ratio of anti-TNF-to-TNF in tissue was highest in uninflamed areas and lowest in severely inflamed areas. Patients with active mucosal disease had a higher rate of serum to tissue drug level mismatch when compared to those in remission (73.3% vs 33.3%, respectively; p=0.03).
Our data suggest that local tissue inflammation characterised by high levels of TNF serves as a sink for anti-TNF. We further postulate that some patients with high serum anti-TNF levels have active disease because tissue levels of anti-TNF are insufficient to neutralise local TNF production.
本研究旨在评估血清和肠道抗肿瘤坏死因子（TNF）水平之间的相关性，及其与内镜疾病活动度和 TNF 水平的关系。
30 例接受英夫利昔单抗或阿达木单抗治疗的克罗恩病或溃疡性结肠炎患者的横断面研究。为每位患者采集血清样本与组织活检相匹配。记录每个组织样本的内镜和组织学疾病活动度。
血清和组织中的抗 TNF 之间存在显著正相关（r=0.3920，p=0.002），尤其是在无炎症组织中（r=0.50，p<0.001），但与有炎症的组织样本无关（r=0.19，p=0.54）。组织中抗 TNF 浓度与内镜炎症程度相关，但严重炎症组织中的抗 TNF 水平再次较低（组织中正常化抗 TNF 的平均浓度：无炎症=0.93，轻度=2.17，中度=13.71，严重=2.2 炎症（p=0.0042））。组织中抗 TNF 与 TNF 的比值在无炎症区域最高，在严重炎症区域最低。与缓解期患者相比，有活动性黏膜疾病的患者血清与组织药物水平不匹配的发生率更高（分别为 73.3%和 33.3%；p=0.03）。
我们的数据表明，以高 TNF 水平为特征的局部组织炎症充当了抗 TNF 的汇流点。我们进一步假设，一些血清抗 TNF 水平较高的患者患有活动期疾病，因为组织中的抗 TNF 水平不足以中和局部 TNF 的产生。
