Author(s): Ishii N, Recke A, Mihai S, Hirose M, Hashimoto T,
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Abstract Type VII collagen (COL7) is a major constituent of the cutaneous basement membrane. Loss of tolerance to COL7 leads to the blistering skin disease epidermolysis bullosa acquisita (EBA). Antibodies to COL7 have also been detected in patients with inflammatory bowel disease (IBD), yet reports on the expression of COL7 in the gut are controversial and a pathogenic relevance of anti-COL7 autoantibodies in IBD has not been demonstrated. We therefore characterized the expression patterns of COL7 in murine gastrointestinal organs and investigated if anti-COL7 antibodies induce an inflammatory response in the gut. COL7 expression was analysed on the mRNA and protein levels. Mice were injected with rabbit anti-murine COL7 IgG (passive EBA) or immunized with a fragment of murine COL7 (active EBA). COL7 was found to be expressed in buccal mucosa, oesophagus, stomach, small intestine, and colon. In addition to skin blistering, in both passive and active EBA, autoantibodies bound to the gastrointestinal basement membrane, fixed complement, and led to recruitment of leukocytes. Furthermore, blister formation was observed in the oesophagus (40\%/38\% of mice in passive/active model), stomach (40\%/63\%), small intestine (20\%/13\%), and colon (20\%/13\%). Compared to control animals, we found a significantly reduced body weight in diseased mice, suggesting that autoantibody-induced gastrointestinal inflammation is clinically relevant. Those observations may help us to understand the co-incidence of IBD with EBA, and vice versa: The inflammatory response in IBD might expose novel antigens (COL7), which leads to the formation of anti-COL7 antibodies. On the contrary, anti-COL7 antibody-induced gastrointestinal inflammation might pave the way for IBD pathogenesis. In summary, our results provide strong evidence that COL7 is expressed in different portions of the gut and that anti-COL7 antibodies induce distinct gastrointestinal tissue damage. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
This article was published in J Pathol
and referenced in Journal of Genetic Syndromes & Gene Therapy