Article Text

Download PDFPDF
Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn’s disease
  1. D Roggenbuck1,
  2. G Hausdorf2,
  3. L Martinez-Gamboa2,
  4. D Reinhold3,
  5. T Büttner1,
  6. P R Jungblut4,
  7. T Porstmann5,
  8. M W Laass6,
  9. J Henker6,
  10. C Büning7,
  11. E Feist2,
  12. K Conrad8
  1. 1
    GA Generic Assays GmbH, Dahlewitz, Germany
  2. 2
    Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
  3. 3
    Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  4. 4
    Max Planck Institute for Infection Biology, Berlin, Germany
  5. 5
    Seramun Diagnostica GmbH, Heidesee, Germany
  6. 6
    Clinic of Pediatrics, Technical University Dresden, Dresden, Germany
  7. 7
    Department of Gastroenterology, Hepatology, and Endocrinology, Charité Universitätsmedizin Berlin, Berlin, Germany
  8. 8
    Institute of Immunology, Technical University Dresden, Dresden, Germany
  1. Correspondence to Dr K Conrad, Institute of Immunology, Technical University Dresden, Fetscherstraße 74, 01307 Dresden, Germany; k_conrad{at}


Backround and aims: The aetiopathogenesis of Crohn’s disease, an inflammatory bowel disease (IBD), is not yet fully understood. Autoimmune mechanisms are thought to play a role in the development of Crohn’s disease, but the target antigens and the underlying pathways have not been sufficiently identified.

Methods: Based on data from immunoblotting and matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry, the major antigenic target of pancreatic autoantibodies (PABs), which are specific for Crohn’s disease, was identified. Specificity of autoantibody reactivity was confirmed by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) using purified rat and human recombinant GP2 synthesised in transiently transfected mammalian HEK 293 cells. Real-time polymerase chain reaction (rt-PCR) and IIF were used to detect mRNA and antigen localisation in human colon biopsies.

Results: The major zymogen granule membrane glycoprotein 2 (GP2) was identified as the autoantigen of PABs in Crohn’s disease. PAB-positive sera from patients with Crohn’s disease (n = 42) displayed significantly higher IgG reactivity to rat GP2 in ELISA than either PAB-negative sera (n = 31), or sera from patients with ulcerative colitis (n = 49), or sera from blood donors (n = 69) (p<0.0001, respectively). Twenty-eight (66%) and 18 (43%) of 42 PAB-positive sera demonstrated IgG and IgA reactivity to human recombinant GP2 in IIF, respectively. Patients with PAB-negative Crohn’s disease (n = 31) were not reactive. GP2 mRNA transcription was significantly higher in colon biopsies from patients with Crohn’s disease (n = 4) compared to patients with ulcerative colitis (n = 4) (p = 0.0286). Immunochemical staining confirmed GP2 expression in human colon biopsies from patients with Crohn’s disease.

Conclusion: Anti-GP2 autoantibodies constitute novel Crohn’s disease-specific markers, the quantification of which could significantly improve the serological diagnosis of IBD. The expression of GP2 in human enterocytes suggests an important role for anti-GP2 response in the pathogenesis of Crohn’s disease.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding This work was supported by the Brandenburg Ministry of Economics and European Union grant 80130073.

  • Competing interests DR is a shareholder of GA Generic Assays GmbH. TP is a shareholder of both Seramun Diagnostica GmbH and GA Generic Assays GmbH. Both companies are diagnostic manufacturers. The remaining authors have no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Ethics approval This study was approved by the local ethics committee of the Medical Faculty, Technical University Dresden, on 3 May 2007. The animals used in this study were handled according to German regulations concerning the protection of animals.

Linked Articles

  • Digest
    BMJ Publishing Group Ltd and British Society of Gastroenterology