Autoantibodies and an immune-based rat model of inflammatory bowel disease

Abstract

The exact causes of inflammatory bowel disease (IBD) are not yet fully defined. From a vast body of literature, we know that the immune response has long been involved in the pathogenesis of IBD, including both ulcerative colitis and Crohn’s disease. A variety of specific alterations can lead to immune activation and inflammation directed to the colon, as revealed by some animal models. Current research has focused on the role of antibodies in downstream events and mechanisms of autoimmunity and inflammation. It is not well known whether the production of antibodies is a serologic consequence of IBD, or if it is a result of barrier dysfunction induced by inflammation. Here, we present a new hypothesis to distinguish the complex links between genetic susceptibility, barrier dysfunction, commensal and pathologic microbial factors and inflammatory response (especially autoantibodies) in the pathogenesis of IBD. To ascertain the hypothesis, we developed a pilot model with the concept of the presence of antibodies against enteric bacterial antigens in IBD. Results confirmed our hypothesis. Our hypothesis suggests the possibility of subcutaneous vaccination of animals with administration of all or specific enteric bacterial antigens.

Keywords: Inflammatory bowel disease rat model, Pathogenesis, Barrier dysfunction, Microbial factor

Core tip: We present a new hypothesis to distinguish the complex links between genetic susceptibility, barrier dysfunction, commensal and pathologic microbial factors and inflammatory response (especially autoantibodies) in the pathogenesis of inflammatory bowel disease (IBD). In our hypothesis, we suggest that prior activation of adaptive immunity against microbial flora antigens could initiate an IBD-like chronic inflammation if something like ethanol disturbs barrier function. If this hypothesis is supported with further experiments, it would illustrate unknown aspects of IBD pathogenesis. On this basis, we have developed a new immune-based model of IBD with the presence of antibodies against enteric bacterial antigens.