Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease

Background-Crohn's disease is a familial disorder, and antiglycan antibodie s to the cell wall mannan of Saccharomyces cerevisiae (ASCA) are highly cor related with Crohn's disease. Aims-To determine whether there is a familial pattern for expression of ser um levels of anti-mannan Ig, and whether this trait is expressed in clinica lly unaffected Crohn's disease family members. Methods-349 patients with Crohn's disease, 87 Crohn's disease affected rela tives, 333 inflammatory bowel disease (IBD) free relatives, 58 spouses, and 190 healthy control patients were studied. Serum IgG and IgA binding activ ity to S cerevisiae cell wall mannan was quantitated by ELISA. Results-A high percentage of patients with Crohn's disease (51.9%) and affe cted family members (56.3%) were seropositive for anti-mannan Ig, compared with the normal control population (3.7%). Seropositive: and seronegative p henotypes of Crohn's disease probands were correlated among all affected re latives, and this association was stronger in affected first degree relativ es. Statistical intraclass correlations of quantitative anti-mannan Ig leve ls revealed significantly less variation within, rather than between famili es. A significant familial aggregation was observed for affected relatives; this was even stronger for unaffected relatives. While a significant famil ial aggregation was observed among unaffected siblings pairs, there was no significant correlation among marital pairs. Conclusion-Results show that antimannan Ig in family members affected and u naffected with Crohn's disease is a familial trait for both affected and un affected relatives. The lack of concordance in marital pairs indicates that familiality is due in part to a genetic factor or childhood environmental exposure.