Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Inflamm Bowel Dis. 2013 Feb;19(2):321-31. doi: 10.1097/MIB.0b013e318280eade.
Easily measured and clinically useful biomarkers for inflammatory bowel disease (IBD) are required to advance patient care. We previously reported that the agalactosyl fraction among fucosylated IgG oligosaccharides is increased in IBD, especially Crohn's disease (CD). The present study aimed to establish a simple detection system for aberrant glycosylated IgG based on lectin-oligosaccharide interactions.
Lectins with higher affinity to serum IgG from IBD patients than healthy volunteers (HV) were screened by lectin microarray. Binding of selected lectins to agalactosyl IgG was definitively confirmed using step-by-step glycosidase treatment. Using the selected lectins, a lectin-enzyme-linked immunosorbent assay system was established and its clinical utility was investigated in a total of 410 (249 Japanese and 161 American) IBD patients, disease controls, and HVs.
Agaricus bisporus Agglutinin (ABA) and Griffonia simplicifolia Lectin-II (GSL-II) had higher affinity for serum agalactosyl IgG from IBD patients, especially those with CD, compared to HV. Agalactosyl IgG levels measured by a lectin-enzyme immunoassay (EIA) with ABA or GSL-II were significantly increased in CD compared with HV and disease controls. Agalactosyl IgG levels significantly correlated with disease activity, showed higher predictability of therapeutic outcomes for CD than C-reactive protein levels, and exhibited higher specificity for diagnosing IBD in combination with anti-Saccharomyces cerevisiae antibody (ASCA). Validation analysis showed that agalactosyl IgG levels were significantly increased in Japanese and American CD patients.
A lectin-EIA for agalactosyl IgG is a novel biomarker for IBD, especially in patients with CD.
为了推进患者护理，我们需要易于测量且对炎症性肠病（IBD）具有临床实用价值的生物标志物。我们之前报道过，在糖基化 IgG 寡糖中，岩藻糖基化的部分在 IBD 中增加，尤其是在克罗恩病（CD）中。本研究旨在建立一种基于凝集素-寡糖相互作用的简单检测异常糖基化 IgG 的方法。
通过凝集素微阵列筛选出与 IBD 患者血清 IgG 结合亲和力高于健康对照者（HV）的凝集素。通过逐步糖苷酶处理，明确证实所选凝集素与半乳糖基 IgG 的结合。使用选定的凝集素，建立了凝集素-酶联免疫吸附测定（ELISA）系统，并在总共 410 名（249 名日本人和 161 名美国人）IBD 患者、疾病对照者和 HV 中研究了其临床应用。
双孢蘑菇凝集素（ABA）和相思豆凝集素-II（GSL-II）与 IBD 患者，尤其是 CD 患者的血清半乳糖基 IgG 结合亲和力更高，与 HV 相比。与 HV 和疾病对照者相比，ABA 或 GSL-II 的凝集素酶免疫测定（EIA）测定的半乳糖基 IgG 水平在 CD 中显著升高。半乳糖基 IgG 水平与疾病活动度显著相关，对 CD 的治疗结果预测性高于 C 反应蛋白水平，与抗酿酒酵母抗体（ASCA）联合使用对诊断 IBD 具有更高的特异性。验证性分析表明，日本和美国 CD 患者的半乳糖基 IgG 水平显著升高。
半乳糖基 IgG 的凝集素-EIA 是 IBD 的一种新型生物标志物，尤其是在 CD 患者中。
