Connective tissue changes in ileal Crohn's disease: Relationship to disease phenotype and ulcer-associated cell lineage

PURPOSE: Abnormalities of enteric collagen and smooth-muscle cell content hare been documented in Crohn's disease. We studied the relationships among connective tissue changes, disease "type," and other disease features using immunohistochemistry and image analysis. METHODS: Twenty consecutive ileal resections for Crohn's disease and ten normal terminal ileal specimens were evaluated using conventional histopathologic examination. Monoclonal antibodies to smooth-muscle actin and Type III collagen fibers were used to determine the percentage area of the submucosa occupied by these constituents using image analysis. RESULTS: There were no significant differences in smooth-muscle content among stenosed, perforated, and ulcerated specimens. There was a significantly increased submucosal Type III collagen content in stenosed vs, other types. The only factor that correlated with smooth muscle cell content was the amount of ulcer-associated cell lineage present. CONCLUSIONS: Increased deposition of Type III collagen fibers rather than smooth-muscle proliferation is associated with a stenotic phenotype. Loss of Type III collagen fibers may play a role in the development of perforating complications. We hale found no evidence that smooth-muscle cells are the source of Type III collagen fiber production although there is evidence that ulcer-associated cell lineage may be related to the stimulus leading to submucosal neomuscularization.