Ulcerative colitis specific cytotoxic IgG-autoantibodies against colonic epithelial cancer cells

Serum antibodies cytotoxic to the colon cancer cell line RPMI 4788 were studied in 42 patients with ulcerative colitis, 61 patients with Crohn's disease, 27 patients with other inflammatory diseases (disease-controls) and 22 healthy controls. Cytotoxicity of antibodies towards RPMI 4788 was studied by means of a chromium release assay using peripheral blood mononuclear leucocytes of healthy subjects as effector cells. Using a four hour antibody dependent cell mediated cytotoxicity assay sera from 29% of ulcerative colitis patients contained antibodies cytotoxic for the target, while only 3% of the Crohn's patients and 6% of the disease controls and non of the healthy controls were positive. When an 18 hour assay was applied, however, not only 40% of ulcerative colitis patients, but also 14% of Crohn's patients and 21% of disease controls were found positive. The reactive antibody in the four hour assay was mainly of the IgG class, which points at a classical antibody dependent cell mediated cytotoxicity mechanism. In the 18 hour cytotoxic assay IgG and particularly IgM antibodies were found to be reactive. This suggests that in the latter case other cellular cytotoxic mechanism might be involved. There was a significant inverse correlation between the appearance of the ulcerative colitis restricted IgG-anticolon epithelial cell antibodies (four hour assay) and the disease activity (p less than 0.01). Absorption studies showed that the reactive antigen is not specific for ulcerative colitis colonic tissue, but is similarly found in Crohn's bowel tissue, and to a lower extent in normal bowel, liver and kidney. The reactive antigen, however, could not be detected in brain and lymphoblastoid cells.