Study objective: To assess whether healthy members of families of patients with inflammatory bowel disease share an immune reactivity to gut epithelial cell antigens.
Design: Assessment of immune reactivity against epithelial-cell-associated components (ECAC).
Methods: Detection of specific anti-ECAC serum antibodies by antibody-dependent cellular cytotoxicity (percent specific lysis) and by immunoblotting (Western blots).
Patients: Index cases (131) and first-degree relatives in 17 families with 2 or more affected members, and 13 with only 1 member affected.
Main results: Compared with a gastrointestinal disease control group (0.5% +/- 0.8%), specific lysis against ECAC-C (colon-derived) among patients with inflammatory bowel disease was significantly greater in both multiply affected (8.4% +/- 8.2%; P less than 0.01) and singly affected (5.2% +/- 5.4%; P less than 0.05) families. In contrast, specific lysis by patients with other inflammatory processes of the small and large bowel (1.1% +/- 1.4%) or autoimmune disease (0.7% +/- 1.0%) did not differ from that of the gastrointestinal disease control group. Among relatives of patients with inflammatory bowel disease (index cases), specific lysis was also significantly higher than in the control group (4.8% +/- 5.5% for multiply affected, P less than 0.01, and 4.3% +/- 5.5% for singly affected, P less than 0.05). Relatives of patients with chronic inflammatory liver disease had a level of lysis (0.6% +/- 0.9%) similar to that of controls. The prevalence of antibodies to ECAC-C was 69.7% among patients with chronic inflammatory bowel disease, and 55.7% among relatives; both prevalences were significantly higher than that of the control group (8.0%, P less than 0.001). Using small-bowel-derived ECAC, the prevalence of antibodies among patients with inflammatory bowel disease and relatives was also significantly higher than that of controls. Reactivity of sera was directed to a 160- and a 137-kilodalton macromolecule.
Conclusions: Immune sensitization to intestinal epithelial antigens is common in families with chronic inflammatory bowel disease; its high frequency among asymptomatic relatives suggests it may represent a primary phenomenon, perhaps predisposing individuals to gut tissue injury.