Anti-Saccharomyces cerevisiae antibodies (ASCA), phenotypes of IBD, and intestinal permeability: a study in IBD families

Background: Serologic markers anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies with perinuclear staining (pANCA) have been proposed to study the immunopathogenesis of IBD. Their measurement may allow better phenotyping of the disease and the detection of subclinical disease. Aims: To test the hypothesis that serological markers identify an immunologic trait related to disease susceptibility. We also wanted to test the hypothesis that ASCA is a marker related to abnormal tissue permeation by common antigens. Methods: We studied the prevalence of pANCA and ASCA in a large cohort of sporadic and familial inflammatory bowel diseases and their unaffected relatives and spouses. Kinetics of ASCA was studied and the relationship between ASCA and Cr-51-EDTA intestinal permeation was investigated. Results: ASCA was associated with sporadic Crohn's disease (CD) (63%), with Crohn's patients belonging to pure CD families (62%) and also with their unaffected family members (21%). pANCA was associated with UC (58%). The prevalence of ASCA in CD patients belonging to mixed families was strikingly low (33%), ASCA was a stable marker throughout the disease and was not related to an increased small intestinal permeability. Conclusion: ASCA is strongly associated with familial CD in Belgium, and 21% of healthy family members also display the marker. The association is much weaker in patients belonging to mixed families. ASCA is a stable marker and is not a secondary phenomenon due to increased intestinal permeability