Agglutinins to four strains of anaerobic gram-positive coccoid rods (species of Eubacterium, Peptostreptococcus and Coprococcus) were found in significantly higher frequency in Crohn's disease (CD) than in ulcerative colitis (UC) and in other diseased control subjects and were virtually absent in apparently healthy subjects. When the posterior probability of having CD was calculated on the basis of these agglutination reactions, 64% of patients with CD and 34% of patients with UC but only 10% of diseased controls and none of the healthy controls were regarded as 'probable' or 'definite' cases of CD. However, the posterior probability of CD did not sharply differentiate between CD and UC but indicated chronic inflammatory bowel disease. Factors contributing to the appearance of these agglutinins in CD were also evaluated. The findings would indicate the importance of a damaged intestinal mucosal barrier for the production of these agglutinins, provided the antigens are present in the intestine. No significant differences were observed between the occurrence of antibodies to pseudomonas-like organisms (PLO) in CD and the various control groups. The study could not add further evidence to the hypothesis of a possible aetiopathogenic role of PLO in CD.
SUMMARY 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 ofa 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<001). 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.About 25 years ago Broberger and Perlmann described haemagglutinating serum antibodies to antigens extracted from human colonic tissue2 as well as antibodies reacting with colonic antigen in situ3 in patients with ulcerative colitis (UC). These antibodies were shown to be autoantibodies.17 While the autoantibodies which were detected by means of immunofluorescence studies on human colon tissue seemed specific for UC, antibodies to germ free rat colon tissue were also found in sera of patients with Crohn's disease (CD) in a comparable frequency and even in disease -controls (review in 8). Early in vitro studies were unable to reveal a complement dependent cytotoxicity of these anticolon antibodies
Three serological tests, recommended as being of diagnostic value for Crohn's disease, were evaluated in 39 patients with Crohn's disease and--as controls--in 27 patients with ulcerative colitis, 45 healthy persons and 65 patients with inflammatory diseases other than Crohn's disease or ulcerative colitis. The tests were the determination of (1) serum antibodies to pseudomonas-like organisms (PLO) by means of indirect immunofluorescence; (2) agglutinating serum antibodies to 4 strains of anaerobic gram-positive coccoid rods (species of Eubacterium, Peptostreptococcus and Coprococcus); and (3) serum antibodies to perinuclear antigens in buccal mucosa of Crohn's disease patients by immunofluorescence. The results indicate that the occurrence of high-titer antibodies to PLO is reasonably sensitive for Crohn's disease, but has a low specificity, and that antibodies to perinuclear antigens in buccal mucosa have both low sensitivity and specificity. However, the occurrence of agglutinins to 4 strains of anaerobic grampositive coccoid rods is significantly higher in Crohn's disease than in ulcerative colitis, patients with other diseases and healthy controls. Thus the determination of these agglutinins does not discriminate between Crohn's disease and ulcerative colitis; but it is a serodiagnostic adjunct in the diagnosis of chronic inflammatory bowel diseases.
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