Article Text

other Versions

PDF
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}genericassays.com)
  1. GA Generic Assays GmbH, Germany
    1. Gert Hausdorf (gert.hausdorf{at}charite.de)
    1. Charité Universitätsmedizin Berlin, Germany
      1. Lorena Martinez-Gamboa
      1. Charité Universitätsmedizin Berlin, Germany
        1. Eugen Feist (eugen.feist{at}charite.de)
        1. Charité Universitätsmedizin Berlin, Germany
          1. Thomas Büttner
          1. GA Generic Assays GmbH, Germany
            1. Dirk Reinhold (dirk.reinhold{at}medizin.uni-magdeburg.de)
            1. Otto-von-Guericke University Magdeburg, Germany
              1. Peter R Jungblut (jungblut{at}mpiib-berlin.mpg.de)
              1. Max Planck Institute for Infection Biology, Germany
                1. Tomas Porstmann (tomas.porstmann{at}seramun.com)
                1. Seramun Diagnostica GmbH, Germany
                  1. Martin W Laass (martin.laass{at}uniklinikum-dresden.de)
                  1. Clinic of Pediatrics, Germany
                    1. Carsten Büning
                    1. Charité Universitätsmedizin Berlin, Germany
                      1. Jobst Henker (jobst.henker{at}uniklinikum-dresden.de)
                      1. Clinic of Pediatrics, Germany
                        1. Karsten Conrad (k_conrad{at}mail.zih.tu-dresden.de)
                        1. Institute of Immunology, Germany

                          Abstract

                          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.

                          Statistics from Altmetric.com

                          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.

                          Linked Articles