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Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn’s disease
  1. Dirk Roggenbuck (dirk.roggenbuck{at}
  1. GA Generic Assays GmbH, Germany
    1. Gert Hausdorf (gert.hausdorf{at}
    1. Charité Universitätsmedizin Berlin, Germany
      1. Lorena Martinez-Gamboa
      1. Charité Universitätsmedizin Berlin, Germany
        1. Eugen Feist (eugen.feist{at}
        1. Charité Universitätsmedizin Berlin, Germany
          1. Thomas Büttner
          1. GA Generic Assays GmbH, Germany
            1. Dirk Reinhold (dirk.reinhold{at}
            1. Otto-von-Guericke University Magdeburg, Germany
              1. Peter R Jungblut (jungblut{at}
              1. Max Planck Institute for Infection Biology, Germany
                1. Tomas Porstmann (tomas.porstmann{at}
                1. Seramun Diagnostica GmbH, Germany
                  1. Martin W Laass (martin.laass{at}
                  1. Clinic of Pediatrics, Germany
                    1. Carsten Büning
                    1. Charité Universitätsmedizin Berlin, Germany
                      1. Jobst Henker (jobst.henker{at}
                      1. Clinic of Pediatrics, Germany
                        1. Karsten Conrad (k_conrad{at}
                        1. Institute of Immunology, Germany


                          Backround and aims: The aetiopathogenesis of Crohn’s disease (CD), an inflammatory bowel disease (IBD), is not yet fully understood. Autoimmune mechanisms are thought to play a role in the development of CD, 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 (PAB), which are specific for CD, was identified. Specificity of autoantibody reactivity was confirmed by enzyme-linked immunosorbent assays (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 PAB in CD. PAB-positive CD patient sera (n=42) displayed significantly higher IgG reactivity to rat GP2 in ELISA than PAB-negative sera (n=31), ulcerative colitis (UC) patient sera (n=49), and blood donor sera (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 CD (n=31) were not reactive. GP2 mRNA transcription was significantly higher in colon biopsies from CD patients (n=4) compared to UC patients (n=4) (p=0.0286). Immunochemical staining confirmed GP2 expression in human colon biopsies from CD patients.

                          Conclusion: Anti-GP2 autoantibodies constitute novel CD-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 CD.

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