Serum zymogen glycoprotein 2 antibodies (anti-GP2) in patients with inflammatory bowel disease

Czech version

Authors: K. Malíčková ¹; D. Ďuricová ²; M. Bortlík ²; L. Hrdlička ²; N. Machková ²; M. Lukáš ^1,2
Authors‘ workplace: Ústav lékařské biochemie a laboratorní diagnostiky 1. LF UK a VFN v Praze ¹; Klinické a výzkumné centrum pro idiopatické střevní záněty ISCARE a 1. LF UK v Praze ²
Published in: Gastroent Hepatol 2013; 67(1): 10-16
Category: IDB: Original Article

Overview

Purpose of the study:
The aim of the study is to examine the incidence and significance of serum antibodies against zymogen glycoprotein 2 (anti-GP2) in patients with inflammatory bowel disease (IBD).

Methods:
Eighty-one patients with IBD were examined, 66 patients with Crohn’s disease (CD) and 15 with ulcerative colitis (UC); there was also a control group of 20 patients with untreated coeliac disease and 50 healthy blood donors. All examined patients with IBD were treated with infliximab. Analyses of anti-GP2 IgG/IgA were performed in samples from week 0 (W0) and week 10 (W10) of the treatment.

Results:
Anti-GP2 in at least one isotype were found in 52% of patients with CD, but only in 13% of patients with UC (p = 0.007). In both control groups, the incidence of anti-GP2 was minimal. Compared to UC patients, individuals with CD achieved significantly higher concentrations of anti-GP2 (p = 0.001 for anti-GP2 IgG at W0 and p < 0.001 for anti-GP2 IgA at W0). No significant changes in concentrations of autoantibodies were observed during 10 weeks of the biological treatment. No evidence of anti-GP2 IgG/IgA association with gender, age, location or type of IBD, or with the activity of the disease was proven. The only significant correlation was found in anti-GP2 IgA with CD damage when stricturing and fistulizing form was related to more frequent incidence and higher anti-GP2 IgA titres.

Conclusions:
Anti-GP2 occure in approximately half of patients with CD. The incidence of anti-GP2 does not correlate with CD location, form or type of the alimentary tract damage; it is not related to the disease activity and concentrations of autoantibody concentrations do not change significantly during the IBD biological treatment.

Key words:
inflammatory bowel diseases – autoantibodies – GP2 protein – biological therapy

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
10. 1. 2013

Accepted:
19. 1. 2013

Sources

1. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet 2007; 369(9573): 1627–1640.

2. Stocker W, Otte M, Ulrich S et al. Autoimmunity to pancreatic juice in Crohn’s disease. Results of an autoantibody screening in patients with chronic inflammatory bowel disease. Scand J Gastroenterol 1987; 139 (Suppl): 41–52.

3. Klebl FH, Bataille F, Huy C et al. Association of antibodies to exocrine pancreas with subtypes of Crohn’s disease. Eur J Gastroenterol Hepatol 2005; 17(1): 73–77.

4. Desplat-J´ego S, Johanet C, Escande A et al. Update in Anti- Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: results of a multicenter study. World J Gastroenterol 2007; 13(16): 2312–2318.

5. Roggenbuck D, Hausdorf G, Martinez-Gamboa L et al. Identification of GP2, the major zymogen granulemembrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn’s disease. Gut 2009; 58(12): 1620–1628.

6. Fukuoka SI, Freedman SD, Scheele GA. A single gene encodes membrane-bound and free forms of GP-2, the major glycoprotein in pancreatic secretory (zymogen) granule membranes. PNAS 1991; 88(7): 2898–2902.

7. Hase K, Kawano K, Nochi T et al. Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune response. Nature 2009; 462(7270): 226–230.

8. Kraehenbuhl JP, Neutra MR. Epithelial M cells: differentiation and function. Ann Rev Cell Dev Biol 2000; 16: 301–332.

9. Bogdanos DP, Rigopoulou EI, Smyk DS et al. Diagnostic value, clinical utility and pathogenic significance of reactivity to the molecular targets of Crohn’s disease specific-pancreatic autoantibodies. Autoimm Rev 2011; 11(2): 143–148.

10. Pavlidis P, Romanidou O, Roggenbuck D et al. Ileal inflammation may trigger the development of GP2-specific pancreatic autoantibodies in patients with Crohn’s disease. Clin Dev Immunol 2012; 2012: 640835.

11. Roggenbuck D, Humbel RL, Reinhold D et al. Glycoprotein 2 antibodies in inflammatory bowel disease – no association with disease phenotype? J Pediatr Gastroenterol Nutr 2012. [Epub ahead of print].

12. Bogdanos DP, Roggenbuck D, Reinhold D et al. Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and behaviour in younger patients with Crohn’s disease. BMC Gastroenterol 2012, 6; 12: 102.

13. Op De Beéck K, Vermeire S, Rutgeerts P et al. Antibodies to GP2, the major zymogen granule membrane glycoprotein, in inflammatory bowel diseases. Gut 2012; 61(1): 162–164

14. Zbořil V et al. Biologická terapie v léčbě idiopatických střevních zánětů. Praha: Mladá fronta 2012.

15. Lukáš M, Ďuricová D, Bortlík M et al. Doporučení pro podávání biologické terapie u idiopatických střevních zánětů. Čes a Slov Gastroent a Hepatol 2008; 62(5): 285–291.

16. Rindler MJ, Hoops TC. The pancreatic membrane protein GP-2 localizes specifically to secretory granules and is shed into the pancreatic juice as a protein aggregate. Eur J Cell Biol 1990; 53(1): 154–163.

17. Bartoloni C, Guidi L, Pili R et al. Assay, isolation and characterization of circulating immune complexes from serum of gastrointestinal cancer, stage III and IV melanom and chronic inflammatory bowel disease patients. Oncology 1993; 50(1): 27–34.

18. Roggenbuck D, Reinhold D, Wex T et al. Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, are new markers in Crohn’s disease. Clin Chim Acta 2011; 412(9–10): 718–724.