Su1913 Anti-Glycan Antibodies in Relatives of Patients With Crohn's Disease

Abstract

Background: Serum anti-glycan antibodies are a promising tool for differential diagnosis, disease stratification and prediction of Crohn's disease (CD). We assessed the presence of serum anti-glycan antibodies in affected and non-affected relatives of patients with CD and ulcerative colitis (UC). Methods: 393 non-inflammatory bowel disease (IBD)-affected relatives (330 CD and 63 UC relatives) of 169 IBD patients (140 CD and 29 UC patients) as well as 46 healthy controls were tested for the presence of anti-laminarin IgA (Anti-L), anti-chitin IgA (Anti-C), anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-mannobioside IgG (AMCA) and anti-Saccaromyces cervisiae IgG (gASCA) carbohydrate antibodies by ELISA in a blinded fashion. Detailed clinical data of the IBD patients were available. Results:Non-affected relatives of CD patients had lower antibody levels for gASCA, ALCA, Anti-L and Anti-C and a lower quartile sum score (QSS), compared to the affected CD subjects (p<0.01). There was no difference in the levels of the antibodies when comparing first and second degree CD relatives. No similarity could be found for the pattern of positive markers in the affected CD patients compared to the non-affected relatives. In addition the ASCA status or a high versus low QSS of the affected CD patient did not influence the extent of the marker expression in the non-affected CD relative. While the QSS was similar, levels of and positivity for ACCA and AMCA were higher in the non-affected CD relatives compared to healthy controls (p<0.05). A higher proportion of healthy controls were negative for all anti-glycan antibodies compared to the non-affected IBD relatives (p<0.01). In the affected CD patients a positive family history for IBD was linked to higher levels of ACCA (p<0.03) and ALCA (p<0.04) with all other markers being unchanged. Non-affected UC relatives had lower levels of ALCA and Anti-L as well as a lower QSS compared to the affected UC patient. Conclusions: Non-affected relatives of CD patients may show a stronger immune response to glycan epitopes compared to healthy controls. The type of response appears to be distinct from the immune response of the affected CD patient. No difference between first compared to second degree relatives could be found. The presence of the antiglycan-antibodies in non-affected relatives of CD patients may represent the manifestation of a genetic susceptibility to CD. Therefore they might serve as an immunologic risk marker for CD and indicate a family member with an increased risk for developing CD in the future.