Buderus Stephan, Boone James, Lyerly David, Lentze Michael J
University Children's Medical Center, Bonn, Germany.
Dig Dis Sci. 2004 Jun;49(6):1036-9. doi: 10.1023/b:ddas.0000034568.69407.47.
The glycoprotein lactoferrin is found in many body fluids but also in the granules of neutrophilic granulocytes. Fecal lactoferrin levels increase quickly with the influx of leukocytes into the intestinal lumen during inflammation. This biomarker has recently been shown to be a sensitive and specific marker of disease activity in chronic inflammatory bowel disease. Our aim was the determination of fecal lactoferrin as a marker of intestinal inflammation and therapeutic response following infliximab therapy in pediatric patients with Crohn's disease (CD). A total of five patients (ages 10-15 years) with severe Crohn's disease as defined by the Pediatric Crohn's Disease Activity Index (PCDAI) was enrolled in the study. The fecal lactoferrin levels were determined before and after therapy with infliximab by a quantitative lactoferrin ELISA (IBD-SCAN; TechLab, Inc.). Of the five patients on infliximab therapy, three received a single infusion and the remaining two underwent a regime with three maintenance infusions. All five patients responded to infliximab clinically after the first infusion, and in all patients, fecal lactoferrin levels significantly and rapidly decreased from elevated to near baseline in parallel to clinical assessment and the PCDAI. The reduction in fecal lactoferrin at days 7-10 was 93.43 +/- 4.49%, in comparison with the level before infliximab therapy, and correlated with a mean decrease in the PCDAI from 48.50 to 14.0. For the patients followed during multiple infusions, one remained with mild disease and the other reached remission (subjective and PCDAI). Fecal lactoferrin is a sensitive and specific biomarker representing intestinal inflammation and response to therapy in pediatric patients with Crohn's disease. It may be a helpful noninvasive diagnostic tool for monitoring therapeutic efficiency in pediatric IBD patients. Future studies are needed to further establish the relationship between endoscopic changes and the level of fecal lactoferrin as well as the possible role of lactoferrin as being an early and preclinical indicator of relapse.
糖蛋白乳铁蛋白存在于许多体液中,也存在于嗜中性粒细胞的颗粒中。在炎症期间,随着白细胞流入肠腔,粪便乳铁蛋白水平会迅速升高。最近研究表明,这种生物标志物是慢性炎症性肠病疾病活动的敏感且特异的标志物。我们的目的是测定粪便乳铁蛋白,将其作为儿童克罗恩病(CD)患者英夫利昔单抗治疗后肠道炎症和治疗反应的标志物。本研究共纳入了5名根据儿童克罗恩病活动指数(PCDAI)定义为重度克罗恩病的患者(年龄10 - 15岁)。通过定量乳铁蛋白酶联免疫吸附测定法(IBD - SCAN;TechLab公司)测定英夫利昔单抗治疗前后的粪便乳铁蛋白水平。在接受英夫利昔单抗治疗的5名患者中,3名接受了单次输注,其余2名接受了3次维持输注的治疗方案。所有5名患者在首次输注后临床症状均有改善,并且在所有患者中,粪便乳铁蛋白水平与临床评估和PCDAI平行,从升高状态显著且迅速下降至接近基线水平。与英夫利昔单抗治疗前的水平相比,第7 - 10天粪便乳铁蛋白的降低幅度为93.43±4.49%,并且与PCDAI从48.50降至14.0的平均降幅相关。对于接受多次输注治疗的患者,1名患者仍为轻度疾病,另1名达到缓解(主观及PCDAI评估)。粪便乳铁蛋白是一种敏感且特异的生物标志物,可反映儿童克罗恩病患者的肠道炎症及对治疗的反应。它可能是监测儿童炎症性肠病患者治疗效果的一种有用的非侵入性诊断工具。未来需要进一步研究以确定内镜变化与粪便乳铁蛋白水平之间的关系,以及乳铁蛋白作为复发的早期和临床前指标的可能作用。