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Novel immunoassays for detection of CUZD1 autoantibodies in serum of patients with inflammatory bowel diseases

  • Sofia Farkona ORCID logo , Antoninus Soosaipillai , Panagiota Filippou , Christos Liaskos , Dimitrios P. Bogdanos , Eleftherios P. Diamandis and Ivan M. Blasutig EMAIL logo
Published/Copyright: March 27, 2017
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 10

Abstract

Background:

Pancreatic autoantibodies (PABs) are detected in patients with inflammatory bowel disease (IBD). Their prevalence is higher in Crohn’s disease (CrD) than in ulcerative colitis (UC). Glycoprotein 2 (GP2) and, more recently, CUB and zona pellucida-like domain-containing protein 1 (CUZD1) have been identified as target autoantigens of PAB. The clinical utility of CUZD1 autoantibodies has only recently been assessed by indirect immunofluorescence (IIF) assays. In this study, we developed and validated novel immunoassays for the detection of CUZD1 autoantibodies.

Methods:

Recombinant CUZD1 protein was utilized as a solid-phase antigen for the development of two immunoassays for the detection of IgG and IgA CUZD1 autoantibodies. Serum samples from 100 patients with CrD, 100 patients with UC, 129 patients assessed for various autoimmune diseases (vADs) and 50 control individuals were analyzed.

Results:

Two immunofluorometric assays for the detection of IgG and IgA CUZD1-specific antibodies were developed. CUZD1 autoantibodies were detected in 12.5% (25/200) IBD patients, including 16% of patients with CrD and in 9% of patients with UC (CrD vs. UC, p<0.05), compared with 3.1% (4/129) patients suspected of having vADs (CrD vs. ADs, p<0.05; UC vs. ADs, p=0.08). CUZD1 autoantibody positivity was not found to be related to disease location, age of disease onset or disease phenotype.

Conclusions:

This is the first study to describe novel IgA and IgG CUZD1 autoantibody enzyme-linked immunosorbent assay. These immunoassays agree well with standard IIF techniques and can be utilized in multicenter studies to investigate the diagnostic and clinical utility of CUZD1 autoantibodies.

Keywords: autoantibodies; autoimmune; Crohn’s disease; CUZD1; ELISA; immunoassay; inflammatory bowel disease; ulcerative colitis

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009;361:2066–78.10.5005/jp/books/11070_14Search in Google Scholar

2. Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571–607.10.1136/gut.2010.224154Search in Google Scholar PubMed

3. Burger D, Travis S. Conventional medical management of inflammatory bowel disease. Gastroenterology 2011;140: 1827–37.e2.10.1053/j.gastro.2011.02.045Search in Google Scholar PubMed

4. Lewis JD. The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology 2011;140:1817–26.e2.10.1053/j.gastro.2010.11.058Search in Google Scholar PubMed PubMed Central

5. Bossuyt X. Serologic markers in inflammatory bowel disease. Clin Chem 2006;52:171–81.10.1373/clinchem.2005.058560Search in Google Scholar PubMed

6. Papp M, Lakatos PL. Serological studies in inflammatory bowel disease: how important are they? Curr Opin Gastroenterol 2014;30:359–64.10.1097/MOG.0000000000000076Search in Google Scholar PubMed

7. Stocker W, Otte M, Ulrich S, Normann D, Finkbeiner H, Stocker K, 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;139:41–52.10.3109/00365528709089774Search in Google Scholar PubMed

8. Bogdanos DP, Rigopoulou EI, Smyk DS, Roggenbuck D, Reinhold D, Forbes A, et al. Diagnostic value, clinical utility and pathogenic significance of reactivity to the molecular targets of Crohn’s disease specific-pancreatic autoantibodies. Autoimmun Rev 2011;11:143–8.10.1016/j.autrev.2011.09.004Search in Google Scholar PubMed

9. Joossens S, Vermeire S, Van Steen K, Godefridis G, Claessens G, Pierik M, et al. Pancreatic autoantibodies in inflammatory bowel disease. Inflamm Bowel Dis 2004;10:771–7.10.1097/00054725-200411000-00012Search in Google Scholar PubMed

10. Seibold F, Scheurlen M, Muller A, Jenss H, Weber P. Impaired pancreatic function in patients with Crohn’s disease with and without pancreatic autoantibodies. J Clin Gastroenterol 1996;22:202–6.10.1097/00004836-199604000-00010Search in Google Scholar PubMed

11. Lakatos PL, Altorjay I, Szamosi T, Palatka K, Vitalis Z, Tumpek J, et al. Pancreatic autoantibodies are associated with reactivity to microbial antibodies, penetrating disease behavior, perianal disease, and extraintestinal manifestations, but not with NOD2/CARD15 or TLR4 genotype in a Hungarian IBD cohort. Inflamm Bowel Dis 2009;15:365–74.10.1002/ibd.20778Search in Google Scholar PubMed

12. Klebl FH, Bataille F, Huy C, Hofstädter F, Schölmerich J, Rogler G. Association of antibodies to exocrine pancreas with subtypes of Crohn’s disease. Eur J Gastroenterol Hepatol 2005;17:73–7.10.1097/00042737-200501000-00015Search in Google Scholar PubMed

13. Seibold F, Weber P, Jenss H, Wiedmann KH. Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn’s disease. Gut 1991;32:1192–7.10.1136/gut.32.10.1192Search in Google Scholar PubMed PubMed Central

14. Roggenbuck D, Hausdorf G, Martinez-Gamboa L, Reinhold D, Büttner T, Jungblut PR, et al. Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn’s disease. Gut 2009;58:1620–8.10.1136/gut.2008.162495Search in Google Scholar PubMed

15. Komorowski L, Teegen B, Probst C, Aulinger-Stocker K, Sina C, Fellermann K, et al. Autoantibodies against exocrine pancreas in Crohn’s disease are directed against two antigens: the glycoproteins CUZD1 and GP2. J Crohns Colitis 2013;7:780–90.10.1016/j.crohns.2012.10.011Search in Google Scholar PubMed

16. Drabovich AP, Dimitromanolakis A, Saraon P, Soosaipillai A, Batruch I, Mullen B, et al. Differential diagnosis of azoospermia with proteomic biomarkers ECM1 and TEX101 quantified in seminal plasma. Sci Transl Med 2013;5:212ra160.10.1126/scitranslmed.3006260Search in Google Scholar PubMed

17. Christopoulos TK, Diamandis EP. Enzymatically amplified time-resolved fluorescence immunoassay with terbium chelates. Anal Chem 1992;64:342–6.10.1021/ac00028a004Search in Google Scholar PubMed

18. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005;19:Suppl A:5a–36a.10.1155/2005/269076Search in Google Scholar PubMed

19. Pavlidis P, Komorowski L, Teegen B, Liaskos C, Koutsoumpas AL, Smyk DS, et al. Diagnostic and clinical significance of Crohn’s disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies. Clin Chem Lab Med 2016;54:249–56.10.1515/cclm-2015-0376Search in Google Scholar PubMed

Supplemental Material:

The online version of this article (DOI: https://doi.org/10.1515/cclm-2016-1120) offers supplementary material, available to authorized users.

Received: 2016-12-8
Accepted: 2017-2-21
Published Online: 2017-3-27
Published in Print: 2017-8-28

©2017 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2016-1120
Keywords for this article
autoantibodies; autoimmune; Crohn’s disease; CUZD1; ELISA; immunoassay; inflammatory bowel disease; ulcerative colitis

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  1. Frontmatter
  2. Editorials
  3. Reporting LDL-cholesterol levels in the era of intensive lipid management: a clarion call
  4. The challenges of genetic risk scores for the prediction of coronary heart disease
  5. Reviews
  6. Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling
  7. A review of the challenge in measuring and standardizing BCR-ABL1
  8. Mini Review
  9. Challenges in the analysis of epigenetic biomarkers in clinical samples
  10. Opinion Paper
  11. Defining a roadmap for harmonizing quality indicators in Laboratory Medicine: a consensus statement on behalf of the IFCC Working Group “Laboratory Error and Patient Safety” and EFLM Task and Finish Group “Performance specifications for the extra-analytical phases”
  12. Genetics and Molecular Diagnostics
  13. Assessment of EGFR mutation status using cell-free DNA from bronchoalveolar lavage fluid
  14. General Clinical Chemistry and Laboratory Medicine
  15. A survey of patients’ views from eight European countries of interpretive support from Specialists in Laboratory Medicine
  16. Verification of examination procedures in clinical laboratory for imprecision, trueness and diagnostic accuracy according to ISO 15189:2012: a pragmatic approach
  17. Expressing analytical performance from multi-sample evaluation in laboratory EQA
  18. A candidate reference method for serum potassium measurement by inductively coupled plasma mass spectrometry
  19. Practical motives are prominent in test-ordering in the Emergency Department
  20. Technical and clinical validation of the Greiner FC-Mix glycaemia tube
  21. Comparison of pneumatic tube system with manual transport for routine chemistry, hematology, coagulation and blood gas tests
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