Electron microscopic, ultracytochemical and immunohistological observations in Crohn's disease of the ileum and colon

Summary

Immunohisto- and ultracytochemical studies were carried out on surgical and biopsy specimens from 27 patients suffering from Crohn's disease of the ileum or colon. Control specimens were obtained from 16 patients with nonspecific proctitis or neoplastic disorders of the caecum or rectum. Our results suggest that the initial lesions in Crohn's disease are associated with a typical humoral immune response. In non-ulcerated mucosa a uniform increase of IgA-, IgG- and IgM-cells was found (numbers of IgA-cells: IgG-cells ∼14.4), whereas disproportional increases of IgG- and IgE-cells were observed in ulcerated mucosa (IgA:IgG ∼0.7). The IgE-cell multiplication in ulcerated areas suggests the possibility of local hypersensitivity reactions. Macrophages and granulocytes contained IgG, which was also demonstrated in multinucleated giant cells. The granulomas contained extracellular IgG, acid phosphatase and peroxidase. The finding of potentially harmful extracellular lysosomal enzymes may be of pathogenetic significance in view of the hypothesis of Weissmann (1964). Micro-ulcerations of the dome epithelium of hyperplastic Peyer's patches were seen by electron microscopy a finding which can be interpreted as an early lesion through which luminal antigens gain uncontrolled access to Peyer's patches. This could lead to (1.) overstimulation of the local immune system, (2.) disturbance of local immune homeostasis, (3.) imbalanced Ig-production with disproportional increases in IgG and IgE. We were not able to detect Clq or C3 bound to epithelial or vascular basement membranes, and no electron dense deposits were found. Viral particles or bacteria in any of the specimens were not demonstrated by electron microscopy. The type of immune response in Crohn's disease and its pathogenetic significance with remain unclear until more is known about the specificity of the locally produced antibodies.