The intestinal mucosa is challenged with more bacterial antigens than any other tissue in the body. Previous work has indicated that inflammatory bowel disease (IBD) results from maladaptive immune responses to intestinal microbiota. However, identification of microbial antigens underlying such intestinal disorders remains difficult due to the diversity of microflora present in these tissues. Through serological cloning of antigens, Robert Hershberg and colleagues, from the Dendreon Corporation, determined that the dominant antigens that instigate pathogenesis in Crohn disease (CD) are from a family of related novel flagellins, the major protein components of bacterial flagella. They examined sera from colitic C3H/HeJBir mice and found reactivity to 15 flagellin clones. Using recombinant flagellin fragments and ELISA assays, they showed that the amino terminus was the immunoreactive domain. Serological studies confirmed that sera from CD patients had high reactivity against particular flagellins, whereas sera from controls and from patients suffering from another IBD, ulcerative colitis, were nonreactive. These findings underscore the link between the innate immune response and the pathogenesis of IBD and offer leads to the identification of other causal antigens in CD.
TITLE: Bacterial flagellin is a dominant antigen in Crohn disease
Dendreon Corporation, Seattle, Washington, USA.
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