Rediscovery of the anti-pancreatic antibodies and evaluation of their prognostic value in a prospective clinical cohort of Crohn's patients: The importance of specific target antigens [GP2 and CUZD1]

M. Papp, Nora Sipeki, Tamas Tornai, I. Altorjay, Gary L. Norman, Zakera Shums, Dirk Roggenbuck, Kai Fechner, Winfried Stöcker, P. Antal-Szalmás, G. Verès, P. Lakatos

Research output: Article

22 Citations (Scopus)

Abstract

Backgrounds: Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1] belong to protein families involved in gut innate immunity processes and have recently been identified as specific targets of anti-pancreatic autoantibodies [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of novel target-specific PAbs regarding long-term disease course of an adult CD patient cohort. Methods: Sera of 458 consecutive well-characterised IBD patients from a single referral IBD centre were tested by enzyme-linked immunosorbent assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG] and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were available on complicated disease or surgical interventions as well as disease activity and medical treatment during the prospective follow-up [median, 108 months]. Results: Totals of 12.4% and 20.8% of CD patients were positive for IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant difference compared with UC [p <0.01]. Antibody status was stable over time. Agreement among three different anti-GP2 assays was good. Positivity for PAbs, mainly IgA subtypes, predicted a faster progression towards complicated disease course. In Kaplan-Meier analysis, time to surgery or development of perianal disease was associated with anti-GP2 IgA [pLogRank <0.01] or anti-CUZD1 IgA [pLogRank <0.001] positivity, respectively. Anti-CUZD1 IgA remained an independent predictor in the multivariate Cox-regression model (hazard ratio [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p <0.001). Conclusions: The present study has shown that specific PAbs [especially IgA subtype] predict complicated disease course including the development of perianal disease in CD.

Original languageEnglish
Pages (from-to)659-668
Number of pages10
JournalJournal of Crohn's and Colitis
Volume9
Issue number8
DOIs
Publication statusPublished - 2015

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ASJC Scopus subject areas

  • Gastroenterology

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