Immunopathology of human inflammatory bowel disease

Mucosal pIgA, and thereby secretory immunity, are disfavored in IBD as revealed by decreased J-chain expression and strikingly increased IgG production by the mucosal immunocytes in both UC and CD. Moreover, a significant shift from IgA2 to the less-resistant IgA1 subclass takes place. Preferential overproduction of IgG1 is seen in UC; and apical deposits of this isotype on the surface epithelium, together with activated complement, is suggestive of a cytotoxic attack related to a brushborder antigen. Comparison of identical twins, discordant with regard to clinical expression of UC, further suggests that this IgG1 response is genetically determined. The IBD lesions furthermore contain many recently recruited and activated T cells as well as monocyte-like macrophages (L1+CD14+) with elevated capacity for production of proinflammatory cytokines (IL-1 and TNF-α) and ROM. Together all these changes reflect less restricted extravasation of precursor cells because of altered expression of adhesion molecules on the microvasculature. Isolated and cultured intestinal endothelial cells subjected to proinflammatory cytokines show enhanced ICAM-1 expression as well as induction of functional E-selectin and MHC class II molecules with antigen-presenting properties.