Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in aVected and unaVected relatives of patients with Crohn’s disease

Background—Crohn’s disease is a familial disorder, and antiglycan antibodies to the cell wall mannan of Saccharomyces cerevisiae (ASCA) are highly correlated with Crohn’s disease. Aims—To determine whether there is a familial pattern for expression of serum levels of anti-mannan Ig, and whether this trait is expressed in clinically unaVected Crohn’s disease family members. Methods—349 patients with Crohn’s disease, 87 Crohn’s disease aVected relatives, 333 inflammatory bowel disease (IBD) free relatives, 58 spouses, and 190 healthy control patients were studied. Serum IgG and IgA binding activity to S cerevisiae cell wall mannan was quantitated by ELISA. Results—A high percentage of patients with Crohn’s disease (51.9%) and aVected family members (56.3%) were seropositive for anti-mannan Ig, compared with the normal control population (3.7%). Seropositive and seronegative phenotypes of Crohn’s disease probands were correlated among all aVected relatives, and this association was stronger in aVected first degree relatives. Statistical intraclass correlations of quantitative anti-mannan Ig levels revealed significantly less variation within, rather than between families. A significant familial aggregation was observed for aVected relatives; this was even stronger for unaVected relatives. While a significant familial aggregation was observed among unaVected siblings pairs, there was no significant correlation among marital pairs. Conclusion—Results show that antimannan Ig in family members aVected and unaVected with Crohn’s disease is a familial trait for both aVected and unaffected relatives. The lack of concordance in marital pairs indicates that familiality is due in part to a genetic factor or childhood environmental exposure.