Mo1247 Serologic Anti-GP2 Antibodies Are Associated With Strictures and Need for Surgical Resection in Crohn's Disease

Abstract

Background: Crohǹs disease (CD) often leads to serious complications, such as fistulae and strictures as well as need for surgery. Early and prolonged immunosuppressive therapy has the potential to alter the natural history of CD. Several serum markers have been tested for the stratification of CD, but their use in clinical practice is still limited. Recently zymogen granule glycoprotein 2 (GP2)was identified as themajor autoantigen of CD-specific pancreatic autoantibodies. Aims: We tested serologic anti-GP2 antibodies for their association with complications and surgery, disease location, disease activity and age at disease onset in patients with CD in a cross-sectional analysis. Methods: Serum samples from 303 CD patients of a tertiary university hospital (mean age 36.1 years, 52.8% female) were tested for the presence of Anti-GP2 IgA and Anti-GP2 IgG by ELISA. Clinical data on disease location, age at disease onset, clinical disease activity, serum CRP, complications (strictures and fistulae) and surgery were available in a prospectively maintained database. Analysis was performed using Wilcoxon rank sum test and logistic regression analysis. Reported odds ratios (ORs) correspond to 10 unit (U) increase in marker levels. Results: After a median follow-up time from diagnosis of 104.6 [interquartile range (IQR) 58.1,168.1] months 77.6% of the CD patients had a complication (49.2% fistulae, 58.4% stenosis), 72.3% underwent surgery and 85.5% had ileal disease involvement. At time of sample procurement 36.5% had clinically active disease and 51.6% had elevated CRP. Levels of anti-GP2 IgG were linked to complicated CD (p=0.002, area under the curve (AUC) 0.62) and ileal disease location (p=0.004, AUC 0.64). Interestingly, both, anti-GP2 IgA and IgG were associated with the occurrence of stenosis and need for surgery (p ,0.001 p=0.003, AUC 0.62 0.64), but not with fistulizing CD, early disease onset, clinically active disease or elevated CRP. After correction for early disease onset and ileal involvement anti-GP2 IgG levels remained significantly linked to stenosis (OR for 10 U increase in GP2 IgG: 1.07 (95% confidence interval (CI): 1.01, 1.1)) and need for surgery (OR for 10 U increase in GP2 IgG: 1.1 (95% CI: 1.01, 1.2)). If patients had both, strictures and fistulae, the association of anti-GP2 IgG with stricturing CD remained significant after correction for the presence of fistulas (OR for 10 U increase in GP2 IgG: 1.07 (95% CI 1.02, 1.1)). Conclusions: Specific levels of anti-GP2 antibodies are independently associated with stricturing CD and need for surgical intervention. Ongoing studies evaluate anti-GP2 levels for their predictive capabilities, the stability of these markers over time and the combination with genetic markers to assess their use in clinical practice.