Human glycoprotein-2 expressed in Brunner glands - A putative autoimmune target and link between Crohn's and coeliac disease

Dirk Roggenbuck; Alexander Goihl; Mandy Sowa; Steffi Lopens; Stefan Rödiger; Peter Schierack; Karsten Conrad; Ulrich Sommer; Korinna Jöhrens; Robert Grützmann; Dirk Reinhold; Martin W Laass

doi:10.1016/j.clim.2022.109214

Human glycoprotein-2 expressed in Brunner glands - A putative autoimmune target and link between Crohn's and coeliac disease

Clin Immunol. 2023 Feb:247:109214. doi: 10.1016/j.clim.2022.109214. Epub 2023 Jan 4.

Authors

Affiliations

¹ Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany. Electronic address: [email protected].
² Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
³ GA Generic Assays GmbH, Dahlewitz, Germany.
⁴ Medipan GmbH, Dahlewitz, Germany.
⁵ Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.
⁶ Institute of Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁷ Department of Pathology, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ Department of General Surgery, University Hospital of Friedrich-Alexander-University, Erlangen, Germany.
⁹ Department of Pediatrics, University Hospital and Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

PMID: 36608744
DOI: 10.1016/j.clim.2022.109214

Abstract

Glycoprotein 2 (GP2) is an autoantigen in Crohn's (CD) and coeliac disease (CeD). We assessed GP2-isoform (GP2_1-4)-expression in intestinal biopsies of paediatric patients with CD, CeD, ulcerative colitis (UC), and healthy children (HC). Transcription of GP2_1-4 was elevated in proximal small intestine in CeD and CD patients (only GP2_2/4) compared to jejunum (CeD/CD) and large bowel (CD). CeD patients demonstrated higher duodenal GP2_2/4-mRNA levels compared to HC/UC patients whereas CD patients showed higher GP2₄-mRNA levels compared to UC patients. Duodenal synthesis of only small GP2 isoforms (GP2_3/4) was demonstrated in epithelial cells in patients/HC and in Brunner glands (also large isoforms) with a more frequent apical location in CD/CeD patients. All four GP2 isoforms interacted with gliadin and phosphopeptidomannan. Gliadin digestion improved binding to GP2 isoforms. GP2_1-4 binding to CeD/CD-related antigens, elevated duodenal GP2_1-4-mRNA transcription, and GP2-protein secretion in Brunner glands of CeD/CD patients suggest an autoimmune CeD/CD link.

Keywords: Celiac disease; Crohn's disease; Zymogen granule membrane glycoprotein GP2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies
Brunner Glands*
Celiac Disease*
Child
Colitis, Ulcerative* / genetics
Crohn Disease* / genetics
GPI-Linked Proteins
Gliadin
Humans
Protein Isoforms
RNA, Messenger / genetics

Substances

Gliadin
GPI-Linked Proteins
Autoantibodies
Protein Isoforms
RNA, Messenger