cqvip:Background and aims: An increased occurrence of anti- Saccharomyces cerev/s/ae antibodies (ASCA) is reported in unaffected members of families with Crohn’ s disease. Whether ASCA is a familial trait due to genetic factors or is caused by exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population. Patients and methods: ASCA were analysed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD15/NOD2 genotype. Results: ASCA were more common in Crohn’ s disease than in ulcerative colitis (40/70 (57% ) twins v 5/43 (12% ) twins). Associations with ileal Crohn’ s disease, stricturing/ penetrating behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5% ) healthy siblings in discordant monozygotic pairs with Crohn’ s disease compared with 7/27 (26% ) in discordant dizygotic pairs. Using the intraclass correlation coefficient (ICC), no agreement in ASCA titres was observed in discordant twin pairs with Crohn’ s disease, in monozygotic (ICC = - 0.02) or dizygotic (ICC = - 0.26) pairs. In contrast, strong agreement was seen within concordant monozygotic twin pairs with Crohn’ s disease (ICC = 0.76). Conclusions: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn’ s disease. The agreement in ASCA titres within concordant monozygotic twin pairs with Crohn’ s disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that a specific gene(s) other than CARD15/NOD2 determines the level of response and perhaps also specific phenotypic characteristics.
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