Lönnkvist Maria H, Theodorsson Elvar, Holst Mikael, Ljung Tryggve, Hellström Per M
Department of Medicine, Gastroenterology and Hepatology Unit, Karolinska University Hospital Solna, Sweden.
Scand J Gastroenterol. 2011 Apr;46(4):420-7. doi: 10.3109/00365521.2010.539253. Epub 2010 Nov 30.
There is a discrepancy between clinical activity and biomarkers in inflammatory bowel disease. The Harvey-Bradshaw index (HBi) is steadfast to evaluate disease activity. A set of biological markers (high sensitive C-reactive protein [hs-CRP], calprotectin, total nitrite, soluble urokinase Plasminogen Activator Receptor [suPAR], ghrelin and endothelin) are investigated to study inflammatory activity and correlation with HBi during infliximab therapy.
Patients with Crohn's disease (n = 22) were assessed and blood samples drawn before and 1 week after infliximab infusion (5 mg/kg) and repeated after 6 months, and compared to healthy volunteers. Hs-CRP, calprotectin, suPAR, ghrelin and endothelin were analyzed with immunoassays, and total nitrite with Griess-reaction. Results were analyzed with Wilcoxon matched-pairs test, Mann-Whitney test and Spearman correlations.
After the first infusion visit, HBi and calprotectin values decreased while nitrite increased (p < 0.05). At the 6-month visit, pre-infusion index and biomarkers had returned to baseline levels. Post-infusion, again the values of HBi, hs-CRP and calprotectin decreased (p < 0.05). The suPAR levels did not change between pre- and post-infusion periods at either visit. Calprotectin, nitrite and suPAR differed from healthy controls throughout the study (p < 0.05). Endothelin decreased with each treatment but was, like ghrelin, not different from controls. We found HBi to correlate with hs-CRP (Spearman r = 0.32, p < 0.05), but calprotectin did not, neither did nitrate nor suPAR.
Although infliximab ameliorates Crohn's disease symptoms, inflammatory markers are not persistently normalized, indicating a chronic inflammatory condition that may require continued infliximab therapy.
炎症性肠病的临床活动与生物标志物之间存在差异。哈维 - 布拉德肖指数（HBi）在评估疾病活动方面较为可靠。研究一组生物标志物（高敏C反应蛋白[hs-CRP]、钙卫蛋白、总亚硝酸盐、可溶性尿激酶型纤溶酶原激活物受体[suPAR]、胃饥饿素和内皮素），以研究英夫利昔单抗治疗期间的炎症活动及其与HBi的相关性。
对22例克罗恩病患者进行评估，在英夫利昔单抗输注（5mg/kg）前、输注后1周及6个月后采集血样，并与健康志愿者进行比较。采用免疫分析法检测hs-CRP、钙卫蛋白、suPAR、胃饥饿素和内皮素，用格里斯反应检测总亚硝酸盐。结果采用威尔科克森配对检验、曼 - 惠特尼检验和斯皮尔曼相关性分析。
首次输注后，HBi和钙卫蛋白值下降，而亚硝酸盐增加（p<0.05）。在6个月的随访中，输注前指数和生物标志物已恢复至基线水平。再次输注后，HBi、hs-CRP和钙卫蛋白值再次下降（p<0.05）。在两次随访的输注前和输注后期间，suPAR水平均未改变。在整个研究过程中，钙卫蛋白、亚硝酸盐和suPAR与健康对照不同（p<0.05）。内皮素随每次治疗而下降，但与胃饥饿素一样，与对照无差异。我们发现HBi与hs-CRP相关（斯皮尔曼r = 0.32，p<0.05），但钙卫蛋白不相关，硝酸盐和suPAR也不相关。
尽管英夫利昔单抗可改善克罗恩病症状，但炎症标志物并未持续正常化，表明存在慢性炎症状态，可能需要持续的英夫利昔单抗治疗。
