P0938 - Unmasking Crohn's Disease: Novel Anti-Glycan Antibodies Provide 15% Incremental Benefit in Diagnostic Accuracy and Prognostic Value in ASCA-Seronegative Patients

Jane Yang, MD¹, Ato O. Aikins, PhD², David Alfego, PhD², Kelly Chun, PhD^1
1Labcorp, Calabasas, CA; ²Labcorp, Burlington, NC

Introduction: Anti-Glycan Antibodies (AGA), gASCA (Anti-Saccharomyces cerevisiae) together with the more novel ACCA (Anti-chitobioside), ALCA (Anti-laminaribioside), and AMCA (Anti-mannobioside) are antibodies specific to Crohn’s Disease (CD) that target glycans (polysaccharides) found in microorganisms, such as C. albicans and S. cerevisiae and may alter the immune response to fungal dysbiosis. The presence of AGA in patient serum differentiates CD from ulcerative colitis (UC), indeterminant colitis, and non-IBD with about 85% specificity. Moreover, concomitant positivity of 2 or more AGA increases CD specificity ( >95%) and predicts faster progression to more severe disease with strictures and fistulae. This diagnostic accuracy of AGA has been validated by more than a dozen independent, peer-reviewed studies in over 4000 IBD patients.¹ Here, we report more recent utilization and real-life performance of AGA.

Methods: As components of Expanded IBD diagnostic and Crohn’s prognostic profiles, gASCA, ACCA, ALCA, and AMCA are detected in serum by enzyme-linked immunosorbent assays using phophomannan, chitobioside, laminaribioside, and mannobioside. gASCA utilizes an improved purified form of mannan and is comparable to conventional ASCA.

Results: Of a total of 175,935 patient samples, one quarter (25.4%) were positive for at least one AGA (Table 1). Isolated positivity of only one AGA was found in 18.4%. Concomitant positivity of 2 or more AGA occurred in 7.0% of all samples.

Discussion: Serum AGA were frequently positive. One quarter of all samples were positive for at least one AGA supporting their potential usefulness in differentiating CD from UC and non-IBD. Most positivity occurred as one isolated positive AGA (~85% specific for CD). A smaller subset had 2 or more AGA and as such, are associated with a very high specificity ( >95%) for CD as well as an odds ratio of 3 for severe disease and need for abdominal surgery.^1,2 Of note, most samples (88.5%) were seronegative for gASCA, reiterating the limited sensitivity of conventional IBD serology (only pANCA and ASCA). Of 155,665 gASCA-seronegative samples, a substantial number, 24,340 (15.6%), were positive for one or more of the novel AGA (ACCA, ALCA or AMCA). Hence, these findings substantiate the incremental benefit of these novel Anti-Glycan Antibodies in identifying those patients more likely to have CD and its more severe sequelae.
1. Bonneau J et al. Autoimmunity Reviews 2015;14:231-245.
2. Kaul A et al. Inflamm Bowel Dis 2012;18(10):1872-1884.


Disclosures:


Jane Yang, MD¹, Ato O. Aikins, PhD², David Alfego, PhD², Kelly Chun, PhD¹. P0938 - Unmasking Crohn's Disease: Novel Anti-Glycan Antibodies Provide 15% Incremental Benefit in Diagnostic Accuracy and Prognostic Value in ASCA-Seronegative Patients, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.