Institute of Nutritional Medicine, Molecular Gastroenterology, University Hospital Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany.
Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, 48149 Münster, Germany.
Cells. 2019 Jan 21;8(1):78. doi: 10.3390/cells8010078.
Inflammatory bowel disease (IBD) is an umbrella term that comprises Crohn's disease (CD) and ulcerative colitis (UC). Both entities are characterized by a disturbed mucosal immune response and an imbalance of intestinal microbiota composition. The complement system (C) plays a critical role in the detection, and clearance of bacteria and dysregulation of single complement components has been linked to IBD. Here, we asked if the C contributes to distinct subtypes of inflammation observed in CD and UC. We performed systematical expression analyses of the intestinal C in IBD patients and controls. Immunohistochemistry or immunoblot experiments were performed to verify qPCR data. Activity of the three activation pathways of C was studied in sera samples. In CD patients a strong upregulation of the C was observed enabling the definition of unique expression patterns being associated either with remission or active disease. These data were reflected by an enhanced C activation in sera and fecal samples. An excessive mucosal presence of immunoglobulin M (IgM) and CR2/CD21 positive B cells in concert with decreased fecal IgA level was identified in CD patients in remission. These findings point to an exacerbated induction of the intestinal C that may potentially be involved in the etiology of CD.
炎症性肠病(IBD)是一个涵盖性术语,包括克罗恩病(CD)和溃疡性结肠炎(UC)。这两种疾病的特征是粘膜免疫反应紊乱和肠道微生物群落组成失衡。补体系统(C)在细菌的检测和清除中起着关键作用,单个补体成分的失调与 IBD 有关。在这里,我们询问 C 是否有助于 CD 和 UC 中观察到的不同类型的炎症。我们对 IBD 患者和对照者的肠道 C 进行了系统的表达分析。通过免疫组织化学或免疫印迹实验验证 qPCR 数据。研究了 C 的三种激活途径在血清样本中的活性。在 CD 患者中,C 的强烈上调被观察到,这使得能够定义与缓解或活动期疾病相关的独特表达模式。这些数据反映在血清和粪便样本中 C 的激活增强。在缓解期的 CD 患者中,发现了免疫球蛋白 M(IgM)和 CR2/CD21 阳性 B 细胞在粘膜中的过度存在,同时粪便 IgA 水平降低。这些发现表明肠道 C 的诱导过度,这可能与 CD 的病因有关。