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.
Highlights
Due to its main functions in detection, opsonization, and elimination of pathogens, as well as of apoptotic or malignant cells, the complement system is crucial for the efficient clearance of invading bacteria, as well as for intestinal tissue homeostasis [1]
In sigmoidal cDNA samples from hospitalized normal (HN), mRNA expression level of analyzed transcripts were ranked in the following order: CALR, C1R, C1QB, CD55, C3, CD59, C1QA, C1QC, C4A, CD46, CR4, CR3, CFB, C1S, C7, CR2, CR1, CD93, C2, C4BPB, C3AR, C5AR2, C6, C1QBP, C5, and C5AR1
Under active disease conditions, the expression level of following mRNA transcripts was significantly upregulated in inflamed sigmoidal biopsy samples from Crohn’s disease (CD) patients in comparison to colitis control patients: C1QB (5-fold), C1R (6-fold), C3 (4-fold), CFB (5-fold), CR3 (3-fold), C5aR2 (8-fold), and CD93 (6-fold) (Figure 1c)
Summary
Due to its main functions in detection, opsonization, and elimination of pathogens, as well as of apoptotic or malignant cells, the complement system is crucial for the efficient clearance of invading bacteria, as well as for intestinal tissue homeostasis [1]. Uncontrolled and sustained complement activation evokes severe inflammatory processes and results in tissue damage, as seen in inflammatory bowel disease (IBD) [2]. Ulcerative colitis (UC) is mainly restricted to the colon and presents severe mucosal inflammation that is accompanied by ulcerations. Crohn’s disease (CD) is characterized by a discontinuous, transmural inflammation that may affect all layers of the intestine. While IgG mainly activates the classical pathway of the complement system via C1q binding, IgA has no C1q binding site but can activate the lectin, as well as the alternative pathway [6]
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