Crohn's Disease Patients in Remission Display an Enhanced Intestinal IgM⁺ B Cell Count in Concert with a Strong Activation of the Intestinal Complement System

克罗恩病缓解期患者的肠道 IgM⁺ B 细胞计数增强,同时肠道补体系统强烈激活

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作者:Sophie Preisker, Ann-Kathrin Brethack, Arne Bokemeyer, Dominik Bettenworth, Christian Sina, Stefanie Derer

Abstract

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.

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