Antimicrobial glycoprotein 2 (GP2) in gallstones, bile fluid and peribiliary glands of patients with primary sclerosing cholangitis

Steffi Lopens; Peter Schierack; Jenny Krause; Michał Piaszczyński; Robert Król; Robert Staroń; Łukasz Krupa; Krzysztof Gutkowski; Beata Kruk; Michał Grąt; Marek Krawczyk; Waldemar Patkowski; Fabian Glaser; Stefan Rödiger; Kai Grossmann; Jacek Pająk; Piotr Milkiewicz; Frank Lammert; Krzysztof Zieniewicz; Christoph Schramm; Dirk Roggenbuck; Marcin Krawczyk

doi:10.1016/j.cca.2024.119841

Antimicrobial glycoprotein 2 (GP2) in gallstones, bile fluid and peribiliary glands of patients with primary sclerosing cholangitis

Clin Chim Acta. 2024 Aug 15:562:119841. doi: 10.1016/j.cca.2024.119841. Epub 2024 Jul 2.

Authors

Steffi Lopens¹, Peter Schierack², Jenny Krause³, Michał Piaszczyński⁴, Robert Król⁴, Robert Staroń⁵, Łukasz Krupa⁵, Krzysztof Gutkowski⁵, Beata Kruk⁶, Michał Grąt⁷, Marek Krawczyk⁷, Waldemar Patkowski⁷, Fabian Glaser³, Stefan Rödiger², Kai Grossmann⁸, Jacek Pająk⁹, Piotr Milkiewicz¹⁰, Frank Lammert¹¹, Krzysztof Zieniewicz⁷, Christoph Schramm¹², Dirk Roggenbuck¹³, Marcin Krawczyk¹⁴

Affiliations

¹ Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; Medipan GmbH, Dahlewitz, Germany.
² 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.
³ Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ Department of General, Vascular and Transplant Surgery, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland.
⁵ Department of Gastroenterology and Hepatology with Internal Disease Unit, Teaching Hospital No 1 in Rzeszów, Rzeszów, Poland; Medical Department, University of Rzeszów, Rzeszów, Poland.
⁶ Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
⁷ Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
⁸ GA Generic Assays GmbH, Senftenberg, Germany.
⁹ Department of Pathomorphology and Molecular Diagnostics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland.
¹⁰ Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland; Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.
¹¹ Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany; Health Sciences, Hannover Medical School (MHH), Hannover, Germany.
¹² Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹³ 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].
¹⁴ Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland; Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.

PMID: 38964568
DOI: 10.1016/j.cca.2024.119841

Abstract

Background: Glycoprotein-2 (GP2) IgA is a predictor of disease severity in primary sclerosing cholangitis (PSC). We examined GP2's occurrence in the biliary tract, the site of inflammation.

Methods: GP2 was analyzed using ELISA, immunoblotting, mass spectrometry, and immunohistochemistry. The samples included: 20 bile and 30 serum samples from PSC patients, 23 bile and 11 serum samples from patients with gallstone disease (GD), 15 bile samples from healthy individuals undergoing liver-donation surgery (HILD), 20 extracts of gallstones (GE) obtained during cholecystectomy, and 101 blood-donor sera.

Results: Biliary GP2 concentrations were significantly higher in patients with PSC and GD than in HILD (p < 0.0001). Serum GP2 levels were similar in PSC and GD patients, and controls, but lower than in bile (p < 0.0001). GP2 was detected in all 20 GEs. Mass spectrometry identified GP2 in the bile of 2 randomly selected GD and 2 PSC patients, and in none of 2 HILD samples. GP2 was found in peribiliary glands in 8 out of 12 PSC patients, showing morphological changes in acinar cells, but not in GD-gallbladders.

Conclusions: GP2 is present in bile of PSC and GD patients. It is synthesized in the peribiliary glands of PSC patients, supporting a pathogenic role for biliary GP2 in PSC.

Keywords: Bile ducts; Cholangitis; Cholelithiasis; Peribiliary gland; Zymogen granule membrane glycoptotein 2.

MeSH terms

Adult
Aged
Bile* / chemistry
Bile* / metabolism
Cholangitis, Sclerosing* / metabolism
Cholangitis, Sclerosing* / pathology
Female
GPI-Linked Proteins
Gallstones* / chemistry
Gallstones* / metabolism
Gallstones* / pathology
Humans
Male
Middle Aged
Young Adult

Substances

GP2 protein, human
GPI-Linked Proteins