Functional Analysis of Agalactosyl IgG in Inflammatory Bowel Disease Patients

Functional Analysis of Agalactosyl IgG in Inflammatory Bowel Disease Patients
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DOI:
10.1002/ibd.21459
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发表时间:
2011-04-01
影响因子:
4.9
通讯作者:
Hayashi, Norio
Hayashi, Norio
中科院分区:
医学2区
文献类型:
--
作者:
Nakajima, Sachiko;Iijima, Hideki;Hayashi, Norio

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背景:无半乳糖基免疫球蛋白(IG)G在炎症性肠病(IBD)中升高,与类风湿性关节炎(RA)相似。凝集素补体途径显示通过RA中的无半乳糖基IgG与甘露聚糖结合凝集素(MBL)的结合而被激活。IgG agalactosylation在IBD的功能变化,但是,尚未澄清。方法:在59例克罗恩病(CD),64溃疡性结肠炎(UC),和39名健康志愿者(HV)的岩藻糖基化IgG低聚糖(G 0 F/G2 F)和血清MBL水平的无半乳糖/非无半乳糖部分的比例进行了分析。用酶联免疫吸附试验分析MBL水平与血清IgG的相关性。免疫组化法检测肠黏膜MBL的表达。绵羊红细胞(SRBC)的吞噬反应与任一agalactosyl或non-agalactosyl SRBC特异性IgG抗体通过流式细胞仪determined.Results:血清MBL水平之间没有显着差异CD,UC,或HV。CD患者血清MBL水平与克罗恩病活动指数(CDAI)呈负相关。与无半乳糖基IgG相关的MBL水平与非无半乳糖基IgG相关的MBL水平没有差异。与非炎症粘膜相比,炎症粘膜对MBL的免疫反应性较低。SRBC的吞噬活性显着较高的存在下,agalactosyl IgG相比,非agalactosyl IgG.Conclusions:Agalactosyl IgG寡糖增强抗体依赖性的吞噬作用在体外,但没有激活凝集素补体途径。IgG的寡糖改变不仅是IBD的标志物,而且在功能上调节IBD的免疫功能。
Background: Agalactosyl immunoglobulin (Ig) G is increased in inflammatory bowel disease (IBD) similarly to rheumatoid arthritis (RA). The lectin complement pathway is shown to be activated through association of agalactosyl IgG with mannan-binding lectin (MBL) in RA. Functional changes of IgG agalactosylation in IBD, however, have not yet been clarified.Methods: The ratio of the agalactosyl/non-agalactosyl fraction in fucosylated IgG oligosaccharides (G0F/G2F) and serum MBL levels were analyzed in 59 patients with Crohn's disease (CD), 64 ulcerative colitis (UC), and 39 healthy volunteers (HV). The MBL levels associated with serum IgG were analyzed by enzyme-linked immunosorbent assay. MBL expression in the intestinal mucosa was analyzed by immunohistochemistry. Phagocytosis of sheep red blood cells (SRBC) reacted with either an agalactosyl or non-agalactosyl SRBC-specific IgG antibody was determined by flow cytometry.Results: The serum MBL levels were not significantly different among CD, UC, or HV. In patients with CD, the serum MBL levels were negatively correlated with the Crohn's Disease Activity Index (CDAI). The levels of MBL associated with agalactosyl IgG were not different from those associated with non-agalactosyl IgG. Immunoreactivity to MBL was less in the inflamed mucosa compared with the noninflamed mucosa. Phagocytic activity of SRBC was significantly higher in the presence of agalactosyl IgG compared to non-agalactosyl IgG.Conclusions: Agalactosyl IgG oligosaccharides enhanced antibody-dependent phagocytosis in vitro but did not activate the lectin complement pathway. Oligosaccharide alterations of IgG are not only a marker of IBD but also functionally modulate the immune function of IBD.