Antibodies against glycoprotein 2 are novel markers of intestinal inflammation in patients with an ileal pouch

Abstract

Background and aims: The Crohn's disease (CD)-specific pancreatic auto-antibodies (PAB), have been recently identified to target glycoprotein 2 (GP2). Pouchitis is an inflammation of the small bowel developing in up to 60% of ulcerative colitis patients undergoing proctocolectomy and ileal pouch anal anastomosis. Occurrence of CD-specific antibodies was reported to be a predictor of pouchitis. We aimed to assess the prevalence of anti-GP2 antibodies (anti-GP2) in the serum and feces of pouch patients and to correlate them with clinical parameters. Furthermore, we examined mucosal expression of the GP2 protein in the pouch.

Methods: Pouch patients were prospectively recruited and checked for clinical, endoscopic, and laboratory markers of inflammation. IgG and IgA anti-GP2 levels in serum and fecal samples were determined using ELISA. GP2 protein was assessed by immunohistochemistry.

Results: Anti-GP2 was elevated in both serum and fecal samples of patients with inflamed compared to those with non-inflamed pouches and patients with familial-adenomatous polyposis after surgery (p<0.05, respectively). Moreover, patients with CD-like complications exhibited significantly higher anti-GP2 titers than those without CD-like complications (p≤0.01). High levels of anti-GP2 correlated with more frequent bowel movements per day and with the presence of at least one anti-glycan antibody (p≤0.05). GP2 itself was more abundant in the mucosa of patients with chronic pouchitis.

Conclusions: Anti-GP2 exists in the serum and feces of pouch patients and correlates with pouch inflammation, and presence of other serological markers. Thus, anti-GP2 may contribute to better stratification of pouchitis, more-so when the inflammation exhibits CD-like complications.

Keywords: ACCA; ALCA; AMCA; ASCA; Anti-GP2; C-reactive protein; CD; CRP; Crohn's disease; FAP; GP2; Glycoprotein 2; IBD; IPAA; PAB; PDAI; Pouchitis; Serological markers; UC; anti-Saccharomyces cerevisiae antibodies; anti-chitobioside carbohydrate antibodies; anti-laminaribioside carbohydrate antibodies; anti-mannobioside carbohydrate antibodies; familial adenomatous polyposis; glycoprotein 2; ileal pouch anal anastomosis; inflammatory bowel diseases; pancreatic (auto)-antibody; pouchitis disease activity index; ulcerative colitis.