Etiopathogenesis of Inflammatory Bowel Disease

Abstract

Although a variety of infectious agents have been implicated in the pathogenesis of Crohn’s disease (CD) over the past decade, progress has been hampered by inconsistent results and lack of a with CD tissue filtrates, 15-20% of them developed granulomas both at the site of Injection and in the intestinal wall (7). Other investigators were unable to Induce granulomatous lesions in various animal species with CD tissue filtrates (8). Recognizing the difficulties reported by several investigators using conventional animals and noting the uniqueness of athymic T cell deficient nude mice for the study of various parasites, bacteria and viruses (8-10), we used homozygous nude mice to search for a disease specific agent(s) of CD. These mice developed lymphomas and hyperplastic lymph nodes (HLN) following injection of lymph node (11) or intestinal tissue filtrates from patients with CD (12). Injection with homogenates of control lymph nodes and intestinal tissue from a variety of disease controls produced occasional lymphomas (13). We then examined these lymphomas and HLN for the presence of a “CD-specific antigen(s)” by indirect immunofluorescence with CD sera. Preliminary results suggested that serum from patients with CD contains an antibody that recognizes a “CD-antigen(s)” in the CD induced lymphomas and HLN (11). We examined the specificity of the immunologic reaction by testing sera from a large number of patients with CD and other diarrheal diseases such as ulcerative and infectious coiitis (13). Similar observations in athymic nude mice were subsequently made by Pena et al. using CD tissue and CD sera from Dutch patients (14). In this study, the investigators further demonstrated that the immunoreactivlty of the CD sera against the nude mouse lymphoid tissue was not related to lymphocytotoxic antibody known to be present in CD sera (14). In a separate study, CD sera, and not the control sera, reacted with the CD-induced nude mouse lymphomas. However, the CD sera also reacted with the control tissue induced lymphomas (15).