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Antibodies Against Glycoprotein 2 Are Specific Biomarkers for Pediatric Crohn’s Disease

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Abstract

Background

Serological markers can assist in accurate differentiation between Crohn’s disease (CD) and ulcerative colitis (UC). One such marker is anti-glycoprotein 2 (anti-GP2) which was shown to be a specific marker for CD in adult patients. The aim of our study was to assess the utility of anti-GP2 and GP2 as biomarkers for pediatric CD, and determine whether they correlate with disease activity.

Methods

Serum samples were tested by ELISA for anti-GP2 isoform 4 IgG and IgA, and also for GP2. Results were correlated with demographic and clinical data.

Results

The cohort consisted of 53 pediatric patients with CD, 42 with UC, and 53 controls. Levels of anti-GP2 were significantly increased in pediatric patients with CD in comparison with patients with UC, and control subjects, with high positive predictive value for both IgG and IgA (97.9% and 82.6%, respectively). While specificity of anti-GP2 IgG and IgA was very high (98.7% and 90.0%, respectively), sensitivity was low (42.0% and 35.5% for IgG and IgA, respectively). In CD, anti-GP2 correlated with disease activity, and decreased in treatment-naïve patients following successful induction therapy. A higher IgA anti-GP2 was also demonstrated in patients with ileo-colonic involvement, and was associated with a younger age. Finally, positive GP2 level was identified in only 1/211 serum samples.

Conclusions

A positive anti-GP2 level is highly associated with CD, while a negative result does not exclude CD. Additional studies are required to determine whether these markers can be used in pediatric patients with CD for risk stratification.

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References

  1. Shouval DS, Rufo PA. The role of environmental factors in the pathogenesis of inflammatory bowel diseases: a review. JAMA Pediatr. 2017;171:999–1005.

    Article  Google Scholar 

  2. Rosen MJ, Dhawan A, et al. Inflammatory bowel disease in children and adolescents. JAMA Pediatr. 2015;169:1053–1060.

    Article  Google Scholar 

  3. Thurgate LE, Lemberg DA, et al. An overview of inflammatory bowel disease unclassified in children. Inflamm Intest Dis. 2019;4:97–103.

    Article  Google Scholar 

  4. Laass MW, Roggenbuck D, et al. Diagnosis and classification of Crohn’s disease. Autoimmun Rev. 2014;13:467–471.

    Article  Google Scholar 

  5. Zhang Z, Li C, et al. Anti-Saccharomyces cerevisiae antibodies associate with phenotypes and higher risk for surgery in Crohn’s disease: a meta-analysis. Dig Dis Sci. 2012;57:2944–2954. https://doi.org/10.1007/s10620-012-2244-y.

    Article  PubMed  Google Scholar 

  6. Smids C, Horjus Talabur Horje CS, et al. The value of serum antibodies in differentiating inflammatory bowel disease, predicting disease activity and disease course in the newly diagnosed patient. Scand J Gastroenterol. 2017;52:1104–1112.

    Article  CAS  Google Scholar 

  7. Spencer EA, Davis SM, et al. Serologic reactivity reflects clinical expression of ulcerative colitis in children. Inflamm Bowel Dis. 2018;24:1335–1343.

    Article  Google Scholar 

  8. Kovacs G, Sipeki N, et al. Significance of serological markers in the disease course of ulcerative colitis in a prospective clinical cohort of patients. PLoS One. 2018;13:e0194166.

    Article  Google Scholar 

  9. Mitsuyama K, Niwa M, et al. Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol. 2016;22:1304–1310.

    Article  CAS  Google Scholar 

  10. Reese GE, Constantinides VA, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006;101:2410–2422.

    Article  CAS  Google Scholar 

  11. Stocker W, Otte M, 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 Suppl. 1987;139:41–52.

    Article  CAS  Google Scholar 

  12. Joossens S, Vermeire S, et al. Pancreatic autoantibodies in inflammatory bowel disease. Inflamm Bowel Dis. 2004;10:771–777.

    Article  Google Scholar 

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

    Article  Google Scholar 

  14. Koutroubakis IE, Drygiannakis D, et al. Pancreatic autoantibodies in Greek patients with inflammatory bowel disease. Dig Dis Sci. 2005;50:2330–2334. https://doi.org/10.1007/s10620-005-3056-0.

    Article  PubMed  Google Scholar 

  15. Demirsoy H, Ozdil K, et al. Anti-pancreatic antibody in Turkish patients with inflammatory bowel disease and first-degree relatives. World J Gastroenterol. 2010;16:5732–5738.

    Article  Google Scholar 

  16. Roggenbuck D, Hausdorf G, et al. Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn’s disease. Gut. 2009;58:1620–1628.

    Article  CAS  Google Scholar 

  17. Werner L, Paclik D, et al. Identification of pancreatic glycoprotein 2 as an endogenous immunomodulator of innate and adaptive immune responses. J Immunol. 2012;189:2774–2783.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Deng C, Li W, et al. Diagnostic value of the antiglycoprotein-2 antibody for Crohn’s disease: a PRISMA-compliant systematic review and meta-analysis. BMJ Open. 2017;7:e014843.

    Article  Google Scholar 

  20. Michaels MA, Jendrek ST, et al. Pancreatic autoantibodies against CUZD1 and GP2 Are associated with distinct clinical phenotypes of crohn’s disease. Inflamm Bowel Dis. 2015;21:2864–2872.

    Article  Google Scholar 

  21. Pavlidis P, Komorowski L, et al. Diagnostic and clinical significance of Crohn’s disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies. Clin Chem Lab Med. 2016;54:249–256.

    Article  CAS  Google Scholar 

  22. Roggenbuck D, Reinhold D, et al. Autoimmunity in crohn’s disease-a putative stratification factor of the clinical phenotype. Adv Clin Chem. 2016;77:77–101.

    Article  CAS  Google Scholar 

  23. Degenhardt F, Dirmeier A, et al. Serologic anti-GP2 antibodies are associated with genetic polymorphisms, fibrostenosis, and need for surgical resection in crohn’s disease. Inflamm Bowel Dis. 2016;22:2648–2657.

    Article  Google Scholar 

  24. Levine A, Griffiths A, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011;17:1314–1321.

    Article  Google Scholar 

  25. Papp M, Sipeki N, et al. Rediscovery of the anti-pancreatic antibodies and evaluation of their prognostic value in a prospective clinical cohort of crohn’s patients: the importance of specific target antigens [GP2 and CUZD1]. J Crohns Colitis. 2015;9:659–668.

    Article  Google Scholar 

  26. Benchimol EI, Mack DR et al. Incidence, outcomes, and health services burden of very early onset inflammatory bowel disease. Gastroenterology. 2014;147, 803–813 e807; quiz e814–805.

  27. Ghione S, Sarter H, et al. Dramatic increase in incidence of ulcerative colitis and crohn’s disease (1988–2011): a population-based study of french adolescents. Am J Gastroenterol. 2018;113:265–272.

    Article  Google Scholar 

  28. Sorrentino D, Nguyen VQ et al.Capturing the biologic onset of inflammatory bowel diseases: impact on translational and clinical science. Cells. 2019;8.

  29. Rober N, Noss L, et al. Autoantibodies against glycoprotein 2 isoforms in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2017;23:1624–1636.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. Roggenbuck D, Reinhold D, et al. Authors’ response: antibodies to GP2, the major zymogen granule membrane glycoprotein, are specific for Crohn’s disease and may reflect treatment response. Gut. 2012;61:164–165.

    Article  CAS  Google Scholar 

  32. Caneparo V, Pastorelli L, et al. Distinct Anti-IFI16 and anti-GP2 antibodies in inflammatory bowel disease and their variation with infliximab therapy. Inflamm Bowel Dis. 2016;22:2977–2987.

    Article  Google Scholar 

  33. Op De Beeck K, Vermeire S et al. Antibodies to GP2, the major zymogen granule membrane glycoprotein, in inflammatory bowel diseases. Gut. 2012;61, 162–164; author reply 164-165.

  34. Roggenbuck D, Goihl A, et al. Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2. Clin Chem Lab Med. 2017;55:854–864.

    Article  CAS  Google Scholar 

  35. Ohno H, Hase K. Glycoprotein 2 (GP2): grabbing the FimH bacteria into M cells for mucosal immunity. Gut Microbes. 2010;1:407–410.

    Article  Google Scholar 

  36. Werner L, Sturm A, et al. Antibodies against glycoprotein 2 are novel markers of intestinal inflammation in patients with an ileal pouch. J Crohns Colitis. 2013;7:e522–532.

    Article  Google Scholar 

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Correspondence to Lael Werner.

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DR has a management role and is a shareholder of GA Generic Assays GmbH and Medipan GmbH. Both companies are diagnostic manufacturers. The remaining authors have no conflicts of interest to declare.

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Shpoliansky, M., Roggenbuck, D., Pinsker, M. et al. Antibodies Against Glycoprotein 2 Are Specific Biomarkers for Pediatric Crohn’s Disease. Dig Dis Sci 66, 2619–2626 (2021). https://doi.org/10.1007/s10620-020-06589-5

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