Elucidation of pathophysiology for various digestive diseases

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In this study, we tried to elucidate pathophysiology of H.pylori-induced gastyritis, autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) all of which involve immunological responses, and the following results were obtained. (1)In human, patients with gastric ulcer had Th1-predominant immunological response, whereas patients with duodenal ulcer were more polarized to Th2 response. Moreover, in patients with MALT lymphoma, Th2 reaction was remarkable. (2)In mice, severe gastritis developed by HP infection in C57black mice, a typical Th1-type strain, whereas no gastritis could be observed in Balb/c mice, a typical Th2-type strain. On the other hand, by thymectomy, severe gastritis seen in C57black mice disappeared and MALT lymphoma developed in Balb/c mice. Moreover, for MALT lymphoma B cell growth in vitro, in addition to HP presence of HP specific T cells and peripheral blood DC were essential. (3)By using serum of the patient who was negative for anti CAII antibody or anti-lactoferin but with high serum IgG titer, we identified pancreatic trypsin inhibitor as a candidate target for autoantibody in patients with autoimmune pancreatitis. (4)In patients with IBD, serum titiers for anti-Mycobacterium antibody was significantly higher than normal subjects, and involvement of Mycobacterium paratuberculosis infection in pathophysiology of human IBD was suggested. (5)Moreover, involvement of CMV as well as EBV infection in the pathophysiology of IBD was also suggested, and importance of measurement of and comparison of copy numbers of CMV gene in both affected and non-affected colonic site for diagnosis of CMV infection in patients with IBD was indicated. (6)For development of IBD, abnormality of permeability of epithelial barrier and that of regeneration of the epithelium were found to be involved. Accordingly, administration of growth factors such as bFGF, that enhances repair of epithelial cells appeared to be effective for the treatment of IBD.