Loss of tolerance to glycoprotein 2 isoforms 1 and 4 is associated with Crohn's disease of the pouch

Background Zymogen granule glycoprotein 2 (GP2) is a major autoantigen of Crohn's disease-specific pancreatic autoantibodies. Aim To test a link between loss of tolerance to isoforms of GP2 and pouch disorders in a cross-sectional study in ulcerative colitis patients with ileal pouch-anal anastomosis (IPAA). Methods Serum samples of 117 consecutive ulcerative colitis patients after IPAA were tested for presence of Anti-GP2 isoforms 1 (GP2(1)) & 4 (GP2(4)) IgG and IgA as well as anti-Saccaromyces cervisiae (ASCA) IgG and IgA antibodies in a blinded fashion via enzyme-linked immunosorbent assay. Pouch disorders were diagnosed based on clinical, endoscopic, histological and radiographic criteria. Crohn's disease of the pouch was defined as involvement of the small bowel mucosa proximal to the ileal pouch with Crohn's disease, development of perianal complications or pouch fistula more than 3 months after ileostomy closure. Results Positivity and level of Anti-GP2(1) IgG (AUC 0.77; P P = 0.02, respectively), Anti-GP2(4) IgG (AUC 0.74; P P = 0.025, respectively) and Anti-GP2(4) IgA (AUC 0.77; P P = 0.018, respectively) were specifically associated with Crohn's disease of the pouch. Anti-GP2 was not associated with endoscopic or histological pouch disease activity index. Neither positivity nor levels of ASCA IgG (AUC 0.63; P = 0.12 & P = 0.35, respectively) or ASCA IgA (AUC 0.67; P = 0.38 & P = 0.53) were associated with pouch phenotypes. Conclusions The novel anti-GP2(1) and GP2(4) antibodies are associated with Crohn's disease of the pouch in ulcerative colitis patients after IPAA. Serological anti-GP2 antibodies could aid in diagnosis of Crohn's disease of the pouch.