SPECIFIC ANTIBODY-RESPONSE TO OLIGOMANNOSIDIC EPITOPES IN CROHNS-DISEASE

Elevated antibody levels against the yeast Saccharomyces cerevisiae ha ve been reported in sera from patients with Crohn's disease and not wi th ulcerative colitis. The aim of the study was to identify the nature of the epitopes supporting this antibody response. Whole cells from d ifferent S. cerevisiae strains were selected in immunofluorescence ass ay for their ability to differentiate the antibody responses of patien ts with Crohn's disease and ulcerative colitis. Their cell wall phosph opeptidomannans were then tested as antigen in enzyme-linked immunosor bent assay (ELISA) against sera from 42 patients with Crohn's disease, 20 patients with ulcerative colitis, and 34 healthy controls. Graded chemical degradations were performed on the most reactive strain phosp hopeptidomannan. The discriminating epitope was determined through gas -liquid chromatography-mass spectrometry. The greatest discrimination among patients with Crohn's disease, ulcerative colitis, and controls was obtained with Su1, a S. cerevisiae strain used in brewing of beer. ELISA directed against phosphopeptidomannan of this strain was 64% se nsitive and 77% specific for discriminating Crohn's disease versus ulc erative colitis and 71% sensitive and 89% specific for Crohn's disease versus controls, Periodate oxidation and selective degradation demons trated that the most important polysaccharide epitope was shared by bo th the acid-stable and the alkali-labile domains of the phosphopeptido mannan. The determination of oligomannose sequences of S. cerevisiae S u1 phosphopeptidomannans suggested that a mannotetraose, Man(1-->3)Man (1-->2)Man(1-->2)Man, supported the serological response seen in Crohn 's disease. Further identification of the immunogen eliciting this ant ibody response as a marker of the disease may help to understand its e tiology.