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

Abstract

Summary 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 (GP21) & 4 (GP24) 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‐GP21 IgG (AUC 0.77; P < 0.001 & P = 0.02, respectively), Anti‐GP24 IgG (AUC 0.74; P < 0.001 & P = 0.025, respectively) and Anti‐GP24 IgA (AUC 0.77; P < 0.001 to 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‐GP21 and GP24 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.

The search for the Holy Grail: autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia

“…Remarkably, GP2 autoAb occurrence could be linked with de novo CD in patients suffering from severe UC with pouchitis after colectomy and ileal pouch anal anastomosis (IPAA) [79,80]. This underscores a close link of the occurrence of GP2 autoAbs with the change of microbiota within the pathophysiology of CD-like symptoms in a formerly UC-driven inflammatory environment.…”

A Multiparametric Method Improves the Serological Characterization of Inflammatory Bowel Diseases: Preliminary Results from a Multicenter Eastern Europe Study

“…In regard to localization of the disease, ileum [30,31,40] and ileocolon [32,36,39] were most frequently associated with PAB positivity, followed by perianal disease [13,32,36]. Interestingly, an association between the presence of PABs and pouchitis has also been proposed [43], offering a possible explanation of the role of PABs in the pathogenic process of IBD. Another feature of CD frequently associated with PABs in the literature is disease onset at early age [11,31,32,42].…”

A Multiparametric Method Improves the Serological Characterization of Inflammatory Bowel Diseases: Preliminary Results from a Multicenter Eastern Europe Study

“…Although the literature agrees in reporting a low (maximum 40%) prevalence of PAB in CD patients (2, 5-19, 30-32, 36-40), there is a great heterogeneity as regards the correlation with clinical features. If we consider the disease behavior, PAB have been reported to be associated with strictures (2,32,36,41,42). However, some authors have also reported an association with penetrating CD (13,40) and even a negative association with stricturing behavior (8).…”