Kappler Katharina, Lasanajak Yi, Smith David F, Opitz Lennart, Hennet Thierry
Institute of Physiology, University of Zurich, Zurich, Switzerland.
Department of Biochemistry, Emory Comprehensive Glycomics Core, Emory University School of Medicine, Atlanta, GA, United States.
Front Microbiol. 2020 Jul 14;11:1553. doi: 10.3389/fmicb.2020.01553. eCollection 2020.
Inflammatory bowel disease is associated with intestinal dysbiosis and with elevated antibody production toward microbial epitopes. The underlying processes linking the gut microbiota with inflammation are still unclear. Considering the constant induction of antibodies by gut microbial glycans, the aim of this study was to address whether the repertoire of carbohydrate-specific antibodies is altered in Crohn's disease or ulcerative colitis. IgG and IgM reactivities to oligosaccharides representative of mucosal glycans were tested in blood serum from 20 healthy control subjects, 17 ulcerative colitis patients, and 23 Crohn's disease patients using glycan arrays. An increased IgG and IgM reactivity toward fucosylated oligosaccharides was detected in Crohn's disease but not in ulcerative colitis. To address the antibody reactivity to the gut microbiota, IgG binding to members of a complex intestinal microbiota was measured and observed to be increased in sera of patients with Crohn's disease. Based on the elevated reactivity to fucosylated oligosaccharides, gut bacteria were tested for recognition by the fucose-binding lectin. was detected in IgG- and lectin-positive fractions and reactivity of lectin was demonstrated for additional species. IgG reactivity to these species was significantly increased in inflammatory bowel disease patients, indicating that the increased reactivity to fucosylated oligosaccharides detected in Crohn's disease may be induced by fucose-carrying intestinal bacteria. Enhanced antibody response to fucosylated epitopes may have systemic effects by altering the binding of circulating antibodies to endogenous glycoproteins.
炎症性肠病与肠道菌群失调以及针对微生物表位的抗体产生增加有关。将肠道微生物群与炎症联系起来的潜在机制仍不清楚。考虑到肠道微生物聚糖不断诱导抗体产生，本研究的目的是探讨在克罗恩病或溃疡性结肠炎中，碳水化合物特异性抗体库是否发生改变。使用聚糖芯片检测了20名健康对照者、17名溃疡性结肠炎患者和23名克罗恩病患者血清中针对代表粘膜聚糖的寡糖的IgG和IgM反应性。在克罗恩病患者中检测到对岩藻糖基化寡糖的IgG和IgM反应性增加，而在溃疡性结肠炎患者中未检测到。为了研究对肠道微生物群的抗体反应性，测量了IgG与复杂肠道微生物群成员的结合情况，发现克罗恩病患者血清中的结合增加。基于对岩藻糖基化寡糖的反应性升高，检测了肠道细菌对岩藻糖结合凝集素的识别情况。在IgG和凝集素阳性组分中检测到[具体细菌名称未给出]，并且证明了[具体细菌名称未给出]凝集素对其他[具体细菌名称未给出]物种具有反应性。炎症性肠病患者对这些[具体细菌名称未给出]物种的IgG反应性显著增加，表明在克罗恩病中检测到的对岩藻糖基化寡糖的反应性增加可能是由携带岩藻糖的肠道细菌诱导的。对岩藻糖基化表位的抗体反应增强可能通过改变循环抗体与内源性糖蛋白的结合而产生全身效应。
