Associations between cellular energy and pediatric inflammatory bowel disease patient response to treatment

Crohn’s disease (CD) and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of which the etiology and pathogenesis are not completely understood. In paediatric patients, the disease tends to be more severe and aggressive then in adults. Here, we perform a proteomic approach on ascending colon biopsies from 119 pediatric patients to characterize disease pathogenesis and the impacts of treatment. Consistent with previous findings, we report an altered proteome in IBD patients that indicates impaired mitochondrial function. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of proteomes from CD patients before and after therapeutic intervention identified over 100 proteins that are significantly different between patients that responded and those that did not respond to therapy; creatine kinase B was elevated before treatment in patients with mucosal healing after treatment, whereas basigin increased after treatment in responsive patients.

克罗恩病（Crohn’s disease, CD）与溃疡性结肠炎均属于慢性炎症性肠病（inflammatory bowel disease, IBD），其病因及发病机制尚未完全阐明。在儿童患者中，该病的病情往往较成人更为严重且侵袭性更强。本研究采用蛋白质组学方法，对119名儿童患者的升结肠活检组织进行分析，以阐明疾病的发病机制并解析治疗手段的影响。与既往研究结果一致，本研究发现炎症性肠病患者的蛋白质组存在异常，提示线粒体功能受损。基因本体（Gene Ontology, GO）富集分析显示，炎症状态下下调的蛋白质与代谢过程密切相关，而上调的蛋白质则参与蛋白质加工过程。对治疗前后的克罗恩病患者的蛋白质组进行比较后发现，在对治疗产生应答与无应答的患者之间，有超过100种蛋白质的表达存在显著差异：其中，治疗后可实现黏膜愈合的患者，其治疗前的肌酸激酶B（creatine kinase B）表达水平升高；而对治疗应答的患者，其治疗后的basigin表达水平上调。