Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter July 15, 2017

An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice

  • Jan Damoiseaux EMAIL logo , Ingmar Heijnen , Christel Van Campenhout , Catharina Eriksson , Nicole Fabien , Manfred Herold , Renate G. van der Molen , William Egner , Dina Patel , Aresio Plaza-Lopez , Antonella Radice , Marie José Rego de Sousa , Markku Viander and Yehuda Shoenfeld

Abstract

Background:

Detection of anti-neutrophil cytoplasmic antibodies (ANCA) is important for the diagnosis of the ANCA-associated vasculitides (AAV). For AAV, especially ANCA directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are most relevant. ANCA with less well-defined specificities may, however, also be detected in other inflammatory and non-inflammatory conditions.

Methods:

A questionnaire, initiated by the European Autoimmunity Standardisation Initiative (EASI), was used to gather information on methods and testing algorithms used for ANCA in clinical laboratories of 12 European countries (EASI survey).

Results:

Four hundred and twenty-nine responses were included in the EASI survey analysis which revealed differences within countries and between countries. Laboratories overall were poor in adherence to international consensus on ANCA testing. Substantial variation was observed with respect to the use of ANCA indirect immunofluorescence (IIF) in the algorithm, application of distinct methods for MPO- and PR3-ANCA, the daily availability of new ANCA results, and interpretation of test results.

Conclusions:

Awareness of these differences may stimulate further harmonization and standardization of ANCA testing. This may be promoted by an update of the international ANCA consensus and the introduction of international standards.


Corresponding author: Jan Damoiseaux, PhD, Central Diagnostic Laboratory, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands

Acknowledgments

Dr. Caroline Roozendaal (University Medical Center Groningen, The Netherlands) is greatly acknowledged for her help in constructing the original questionnaire. Also, all the members of the national EASI-teams are acknowledged for their collaboration. In Italy EASI is integrated into the Italian Forum on Autoimmune Disease Research (FIRMA). In Switzerland the EASI activities are covered by the Commission of Laboratory Diagnostics of the Swiss Society for Allergology and Immunology (SSAI). In Spain EASI activities are coordinated by the Spanish Group of Autoimmunity (GEAI). Finally, we also thank all the laboratory specialists who returned the completed questionnaire.

  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 of leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: None declared.

References

1. Cohen Tervaert JW, Damoiseaux J. Antineutrophil cytoplasmic autoantibodies: how are they detected and what is their use for diagnosis, classification and follow-up? Clin Rev Allergy Immunol 2012;43:211–9.10.1007/s12016-012-8320-4Search in Google Scholar PubMed

2. Radice A, Bianchi L, Sinico RA. Anti-neutrophil cytoplasmic autoantibodies: methodological aspects and clinical significance in systemic vasculitis. Autoimmun Rev 2013;12:487–95.10.1016/j.autrev.2012.08.008Search in Google Scholar PubMed

3. Csernok E, Moosig F. Current and emerging techniques for ANCA detection in vasculitis. Nat Rev Rheumatol 2014;10:494–501.10.1038/nrrheum.2014.78Search in Google Scholar PubMed

4. Savige J, Gillis D, Benson E, Davies D, Esnault V, Falk RJ, et al. International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol 1999;111:507–13.10.1093/ajcp/111.4.507Search in Google Scholar PubMed

5. Choi HK, Liu S, Merkel PA, Colditz GA, Niles JL. Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies. J Rheumatol 2001;28:1584–90.Search in Google Scholar

6. Beauvillain C, Delneste Y, Renier G, Jeannin P, Subra JF, Chevailler A. Antineutrophil cytoplasmic autoantibodies: how should the biologist manage them? Clin Rev Allergy Immunol 2008;35:47–58.10.1007/s12016-007-8071-9Search in Google Scholar PubMed

7. Kyriakidi KS, Tsianos VE, Karvounis E, Christodoulou DK, Katsanos KH, Tsianos EV. Neutrophil anti-neutrophil cytoplasmic autoantibody proteins: bactericidal increasing protein, lactoferrin, cathepsin, and elastase as serological markers of inflammatory bowel and other diseases. Ann Gastroenterol 2016;29:258–67.10.20524/aog.2016.0028Search in Google Scholar PubMed PubMed Central

8. Liberal R, Mieli-Vergani G, Vergani D. Clinical significance of autoantibodies in autoimmune hepatitis. J Autoimmun 2013;46:17–24.10.1016/j.jaut.2013.08.001Search in Google Scholar PubMed

9. Weiner M, Segelmark M. The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA). Autoimmun Rev 2016;15:978–82.10.1016/j.autrev.2016.07.016Search in Google Scholar PubMed

10. Savige J, Dimech W, Fritzler M, Goeken J, Hagen EC, Jennette JC, et al. Addendum to the International Consensus Statement on testing and reporting of antineutrophil cytoplasmic antibodies. Quality control guidelines, comments, and recommendations for testing in other autoimmune diseases. Am J Clin Pathol 2003;120:312–8.10.1309/WAEPADW0K4LPUHFNSearch in Google Scholar

11. Westman KW, Selga D, Bygren P, Segelmark M, Baslund B, Wiik A, et al. Clinical evaluation of a capture ELISA for detection of proteinase-3 antineutrophil cytoplasmic antibody. Kidney Int 1998;53:1230–6.10.1046/j.1523-1755.1998.00873.xSearch in Google Scholar PubMed

12. Csernok E, Holle J, Hellmich B, Cohen Tervaert JW, Kallenberg CG, Limburg PC, et al. Evaluation of capture ELISA for detection of antineutrophil cytoplasmic antibodies directed against proteinase 3 in Wegener’s granulomatosis: first results from a multicentre study. Rheumatology (Oxford) 2004;43:174–80.10.1093/rheumatology/keh028Search in Google Scholar PubMed

13. Hellmich B, Csernok E, Fredenhagen G, Gross WL. A novel high sensitivity ELISA for detection of antineutrophil cytoplasm antibodies against proteinase-3. Clin Exp Rheumatol 2007;25 (1 Suppl 44):S1–5.Search in Google Scholar

14. Damoiseaux J, Dähnrich C, Rosemann A, Probst C, Komorowski L, Stegeman CA, et al. A novel enzyme-linked immunosorbent assay using a mixture of human native and recombinant proteinase-3 significantly improves the diagnostic potential for antineutrophil cytoplasmic antibody-associated vasculitis. Ann Rheum Dis 2009;68:228–33.10.1136/ard.2007.086579Search in Google Scholar PubMed

15. Roggenbuck D, Buettner T, Hoffmann L, Schmechta H, Reinhold D, Conrad K. High-sensitivity detection of autoantibodies against proteinase-3 by a novel third-generation enzyme-linked immunosorbent assay. Ann NY Acad Sci 2009;1173:41–6.10.1111/j.1749-6632.2009.04649.xSearch in Google Scholar PubMed

16. Damoiseaux J, Vaessen M, Knapen Y, Csernok E, Stegeman CA, Van Paassen P, et al. Evaluation of the FIDIS vasculitis multiplex immunoassay for diagnosis and follow-up of ANCA-associated vasculitis and Goodpasture’s disease. Ann NY Acad Sci 2007;1109:454–63.10.1196/annals.1398.051Search in Google Scholar PubMed

17. Trevisin M, Pollock W, Dimech W, Savige J. Evaluation of a multiplex flow cytometric immunoassay to detect PR3- and MPO-ANCA in active and treated vasculitis, and in inflammatory bowel disease (IBD). J Immunol Methods 2008;336:104–12.10.1016/j.jim.2008.03.012Search in Google Scholar PubMed

18. Kaul R, Johnson K, Scholz H, Marr G. Performance of the BioPlex 2200 Autoimmune Vasculitis kit. Autoimmun Rev 2009;8:224–7.10.1016/j.autrev.2008.07.033Search in Google Scholar PubMed

19. Mahler M, Radice A, Yang W, Bentow C, Seaman A, Bianchi L, et al. Development and performance evaluation of novel chemiluminescence assays for detection of anti-PR3 and anti-MPO antibodies. Clin Chim Acta 2012;413:719–26.10.1016/j.cca.2012.01.004Search in Google Scholar PubMed

20. Damoiseaux JG, Slot MC, Vaessen M, Stegeman CA, Van Paassen P, Tervaert JW. Evaluation of a new fluorescent-enzyme immuno-assay for diagnosis and follow-up of ANCA-associated vasculitis. J Clin Immunol 2005;25:202–8.10.1007/s10875-005-3863-2Search in Google Scholar PubMed

21. Sinico RA, Radice A, Corace C, DI Toma L, Sabadini E. Value of a new automated fluorescence immunoassay (EliA) for PR3 and MPO-ANCA in monitoring disease activity in ANCA-associated systemic vasculitis. Ann NY Acad Sci 2005;1050:185–92.10.1196/annals.1313.019Search in Google Scholar PubMed

22. Rutgers A, Damoiseaux J, Roozendaal C, Limburg PC, Stegeman CA, Tervaert JW. ANCA-GBM dot-blot: evaluation of an assay in the differential diagnosis of patients presenting with rapidly progressive glomerulonephritis. J Clin Immunol 2004;24:435–40.10.1023/B:JOCI.0000029115.79266.aeSearch in Google Scholar

23. Damoiseaux J, Steller U, Buschtez M, Vaessen M, Rosemann A, van Paassen P, et al. EUROPLUS ANCA BIOCHIP mosaic: PR3 and MPO antigen microdots improve the laboratory diagnostics of ANCA-associated vasculitis. J Immunol Methods 2009;348:67–73.10.1016/j.jim.2009.07.001Search in Google Scholar PubMed

24. Sowa M, Grossmann K, Knütter I, Hiemann R, Röber N, Anderer U, et al. Simultaneous automated screening and confirmatory testing for vasculitis-specific ANCA. PLoS One 2014;9:e107743.10.1371/journal.pone.0107743Search in Google Scholar PubMed PubMed Central

25. Avery TY, Bons J, van Paassen P, Damoiseaux J. Diagnostic ANCA algorithms in daily clinical practice: evidence, experience, and effectiveness. Lupus 2016;25:917–24.10.1177/0961203316640921Search in Google Scholar PubMed

26. Damoiseaux J, Csernok E, Rasmussen N, Moosig F, van Paassen P, Baslund B, et al. Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis 2017;76:647–53.10.1136/annrheumdis-2016-209507Search in Google Scholar PubMed

27. Shoenfeld Y, Cervera R, Haass M, Kallenberg C, Khamashta M, Meroni PL, et al. EASI – the European Autoimmunity Standardisation Initiative. Ann NY Acad Sci 2007;1109:138–44.10.1196/annals.1398.016Search in Google Scholar PubMed

28. Molen RG van der, Roozendaal C, Damoiseaux JG. Detection of ANCA in Dutch laboratories: clinical practice in relation to the international consensus and national guidelines (In Dutch). Ned Tijdschr Klin Chem Labgeneesk 2014;39:19–24.Search in Google Scholar

29. Wiik A. Delineation of a standard procedure for indirect immunofluorescence detection of ANCA. APMIS Suppl 1989;6:12–3.Search in Google Scholar

30. Russel KA, Wiegert E, Schroeder DR, Homburger HA, Specks U. Detection of anti-neutrophil cytoplasmic antibodies under actual clinical testing conditions. Clin Immunol 2002;103:196–203.10.1006/clim.2001.5200Search in Google Scholar PubMed

31. Tervaert JW, Damoiseaux J. Fifty years of antineutrophil cytoplasmic antibodies (ANCA) testing: do we need to revise the international consensus statement on testing and reporting on ANCA? APMIS Suppl 2009;127:55–9.10.1111/j.1600-0463.2009.02478.xSearch in Google Scholar PubMed

32. Vermeersch P, Vervaeke S, Blockmans D, Van Hoovels L, Mariën G, Vanmaele H, et al. Determination of anti-neutrophil cytoplasmic antibodies in small vessel vasculitis: comparative analysis of different strategies. Clin Chim Acta 2008;397:77–81.10.1016/j.cca.2008.07.026Search in Google Scholar PubMed

33. Mahler M, Bogdanos D, Pavlidis P, Fritzler MJ, Csernok E, Damoiseaux J, et al. PR3-ANCA: a promising biomarker for ulcerative colitis with extensive disease. Clin Chim Acta 2013;424:267–73.10.1016/j.cca.2013.06.005Search in Google Scholar PubMed

34. Lohse AW. Diagnostic criteria for autoimmune hepatitis: scores and more. Dig Dis 2015;33 Suppl 2:47–52.10.1159/000440709Search in Google Scholar PubMed

35. Stange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A, et al. European evidence-based consensus on the diagnosis and management of ulcerative colitis: definitions and diagnosis. J Crohn’s Colitis 2008;2:1–23.10.1016/j.crohns.2007.11.001Search in Google Scholar

36. Assche G van, Dignass A, Panes J, Beaugerie L, Karagiannis J, Allez M, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohn’s Colitis 2010;4:7–27.10.1016/j.crohns.2009.12.003Search in Google Scholar

37. Csernok E, Damoiseaux J, Rasmussen N, Hellmich B, van Paassen P, Vermeersch P, et al. Evaluation of automated multi-parametric indirect immunofluorescence assays to detect antineutrophil cytoplasmic antibodies (ANCA) in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Autoimmun Rev 2016;15:736–41.10.1016/j.autrev.2016.03.010Search in Google Scholar

38. Westman KW, Bygren PG, Eilert I, Wiik A, Wieslander J. Rapid screening assay for anti-GBM antibody and ANCAs; an important tool for the differential diagnosis of pulmonary renal syndromes. Nephrol Dial Transplant 1997;12:1863–8.10.1093/ndt/12.9.1863Search in Google Scholar

39. de Joode AA, Roozendaal C, van der Leij MJ, Bungener LB, Sanders JS, Stegeman CA. Performance of two strategies for urgent ANCA and anti-GBM analysis in vasculitis. Eur J Intern Med 2014;25:182–6.10.1016/j.ejim.2013.11.011Search in Google Scholar

40. Sowa M, Trezzi B, Hiemann R, Schierack P, Grossmann K, Scholz J, et al. Simultaneous comprehensive multiplex autoantibody analysis for rapidly progressive glomerulonephritis. Medicine (Baltimore) 2016;95:e5225.10.1097/MD.0000000000005225Search in Google Scholar

41. Rutgers A, Heeringa P, Damoiseaux JG, Cohen Tervaert JW. ANCA and anti-GBM antibodies in diagnosis and follow-up of vasculitic disease. Eur J Int Med 2003;14:287–95.10.1016/S0953-6205(03)00097-9Search in Google Scholar

42. Monogioudi E, Hutu DP, Martos G, Sheldon J, Schimmel H, Meroni PL, et al. Development of a Certified Reference Material for myeloperoxidase-anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA). Clin Chim Acta 2017;467: 48–50.10.1016/j.cca.2016.05.031Search in Google Scholar PubMed

Received: 2017-04-07
Accepted: 2017-05-29
Published Online: 2017-07-15
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 26.4.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2017-0306/html
Scroll to top button