Li Xuhang, Conklin Laurie, Alex Philip
Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave, 918 Ross Research Bldg, Baltimore, MD 21205, United States.
World J Gastroenterol. 2008 Sep 7;14(33):5115-24. doi: 10.3748/wjg.14.5115.
Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Sigma) two major oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (SigmaMan3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-like receptors (TLR) 2 and 4, and beta-defensin-1. Furthermore, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and multiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically useful novel diagnostic algorithms by incorporating new technologies in serological biomarker profiling and integrating multiple biomarkers with bioinformatics analysis/modeling are also discussed.
炎症性肠病（IBD）中的血清学生物标志物是用于疾病活动客观评估、早期诊断、预后评估及监测的非侵入性检测项目，其数量正在迅速增加。本综述总结了IBD中的新旧生物标志物，但重点关注新血清学生物标志物（2007年以来发现的）的开发与特性。这些新标志物包括五种新的抗聚糖抗体，即抗壳二糖苷IgA（ACCA）、抗层黏二糖苷IgG（ALCA）、抗甘露二糖苷IgG（AMCA），以及针对化学合成的（西格玛公司）两种主要寡甘露糖表位、Manα-1,3Manα-1,2Man（西格玛甘露糖3）和Manα-1,3Manα-1,2Manα-1,2Man（西格玛甘露糖4）的抗体。这些新生物标志物不仅在区分克罗恩病（CD）、溃疡性结肠炎（UC）、正常及其他非IBD肠道疾病方面，而且在预测疾病累及部位（回肠与结肠）、IBD风险（作为亚临床生物标志物）及疾病进程（并发症和手术风险）方面，都是现有生物标志物的宝贵补充工具。有趣的是，发现包括抗酿酒酵母抗体（ASCA）、ALCA和AMCA在内的抗聚糖抗体的患病率与IBD易感基因如NOD2/CARD15、NOD1/CARD4、Toll样受体（TLR）2和4以及β-防御素-1的单核苷酸多态性（SNP）相关。此外，还观察到基因剂量效应：随着NOD2/CARD15 SNP数量增加，抗聚糖阳性变得更为常见。综述的其他新的血清/血浆IBD生物标志物包括泛素化因子E4A（UBE4A）、CXCL16（一种趋化因子）、抵抗素和载脂蛋白A-IV。本综述还讨论了通过应用蛋白质组学、傅里叶变换近红外光谱和多重酶联免疫吸附测定（ELISA）等新技术（重点是细胞因子/趋化因子分析）在IBD生物标志物发现方面的最新研究。最后，还讨论了通过将新技术纳入血清学生物标志物分析并将多种生物标志物与生物信息学分析/建模相结合来开发更具临床实用性的新型诊断算法的前景。
