Abstract
Pediatric Crohn's disease is a chronic auto inflammatory bowel disorder affecting children under the age of 17 years. A putative etiopathogenesis of Crohn's disease (CD) is associated with disregulation of immune response to antigens commonly present in the gut microenvironment. Heat shock proteins (HSP) have been identified as ubiquitous antigens with the ability to modulate inflammatory responses associated with several autoimmune diseases. The present study tested the contribution of immune responses to HSP in the amplification of autoimmune inflammation in chronically inflamed mucosa of pediatric CD patients. Colonic biopsies obtained from normal and CD mucosa were stimulated with pairs of Pan HLA-DR binder HSP60-derived peptides (human/bacterial homologues). The modulation of RNA and protein levels of induced proinflammatory cytokines were measured. We identified two epitopes capable of sustaining proinflammatory responses, specifically TNF〈 and IFN© induction, in the inflamed intestinal mucosa in CD patients. The responses correlated positively with clinical and histological measurements of disease activity, thus suggesting a contribution of immune responses to HSP in pediatric CD site-specific mucosal inflammation.
Highlights
Crohn’s disease (CD) is a form of chronic auto-inflammatory bowel disease (IBD) characterized by patchy involvement of the intestinal tract
This study addresses the hypothesis that local inflammation is the outcome of inappropriate immune responses to common environmental stimuli, and that such responses contribute to disease activity independently of the events that have triggered the disease [2,4,5]
We have demonstrated in various autoimmune diseases that heat shock proteins (HSP)-derived epitopes are capable of inducing and modulating specific T-cell responses and that such modulation correlates with disease activity [15,18,19]
Summary
Crohn’s disease (CD) is a form of chronic auto-inflammatory bowel disease (IBD) characterized by patchy involvement of the intestinal tract. This study addresses the hypothesis that local inflammation is the outcome of inappropriate immune responses to common environmental stimuli, and that such responses contribute to disease activity independently of the events that have triggered the disease [2,4,5]. Such antigens should be available within both the microbial flora and the target tissue, over-expressed at the site of inflammation [6,7] and strongly antigenic [8,9,10]. A growing body of work [8,11,12,13,14], including our own published findings [15,16,17], implicate that heat shock proteins (HSP) are among the antigens capable of sustaining such immune/autoimmune inflammation
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