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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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IMPACT FACTOR 2017: 3.556

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1437-4331
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Volume 56, Issue 6

Issues

Borderline positive antineutrophil cytoplasmic antibodies (ANCA)-PR3/MPO detection in a large cohort tertiary center: lessons learnt from a real-life experience

Abdulla Watad
  • Department of Medicine ‘B’, Sheba Medical Center, Tel Hashomer, Israel
  • Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel
  • Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nicola L. Bragazzi
  • School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kassem Sharif
  • Department of Medicine ‘B’, Sheba Medical Center, Tel Hashomer, Israel
  • Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Boris Gilburd / Yarden Yavne
  • Department of Medicine ‘B’, Sheba Medical Center, Tel Hashomer, Israel
  • Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dennis McGonagle
  • Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Howard Amital
  • Department of Medicine ‘B’, Sheba Medical Center, Tel Hashomer, Israel
  • Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel
  • Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yehuda Shoenfeld
  • Corresponding author
  • Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel
  • Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-01-29 | DOI: https://doi.org/10.1515/cclm-2017-1053

Abstract

Background:

Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) are the best strategies for antineutrophil cytoplasmic antibodies (ANCA) detection. In a minority of subjects, ELISA-based ANCA testing may result in a borderline positive titre. Therefore, we assessed the clinical significance of such a result.

Methods:

This is a retrospective study, which included all subjects screened for ANCA subtypes (myeloperoxidase (MPO) or proteinase-3 (PR3)) with subsequent identification of borderline positive results, as determined by ELISA and retested using IIF. The demographic, clinical and laboratory data of subjects with borderline positive ANCA test results were extracted from their medical records.

Results:

A total of 14,555 PR3/MPO-ANCA tests were performed with ELISA during the study period (2006–2016). Of the 14,555 PR3-ANCA antibody tests that were performed, 94 were borderline positive (titre 0.9–1.1), and of 14,555 MPO-ANCA antibody tests, 43 were borderline positive (titre 0.9–1.1). The male-to-female ratio was 1:1.08 and the mean age was 50.95±21.79 years. Four MPO-ANCA (9.30%) and 11 PR3-ANCA (11.70%) antibody borderline samples resulted positive on IIF testing. Subjects with borderline positive MPO-ANCA were found to have a poorer outcome in terms of renal failure and the requirement of dialysis.

Conclusions:

Subjects with borderline positive MPO-ANCA and positive p-ANCA (IIF) seem to have a less favorable outcome. Physicians should be aware of these findings and possibly perform a closer follow-up and routine screening for these subjects.

Keywords: ANCA; c-ANCA; ELISA; immunofluorescence; myeloperoxidase; p-ANCA; proteinase-3; vasculitis

References

  • 1.

    Damoiseaux J, Agmon-Levin N, Van Blerk M, Chopyak V, Eriksson C, Heijnen I, et al. From ANA-screening to antigen-specificity: an EASI-survey on the daily practice in European countries. Clin Exp Rheumatol 2014;32:539–46.PubMedGoogle Scholar

  • 2.

    Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol 2016;3:122–33.PubMedCrossrefGoogle Scholar

  • 3.

    Davies DJ, Moran JE, Niall JF, Ryan GB. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br Med J (Clin Res Ed) 1982;285:606.PubMedCrossrefGoogle Scholar

  • 4.

    Castro C, Gourley M. Diagnostic testing and interpretation of tests for autoimmunity. J Allergy Clin Immunol 2010;125(2 Suppl 2):S238–47.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 5.

    Gross WL, Schmitt WH, Csernok E. ANCA and associated diseases: immunodiagnostic and pathogenetic aspects. Clin Exp Immunol 1993;91:1–12.PubMedGoogle Scholar

  • 6.

    Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJ, Nightingale P, Sandoo A, Dimitroulas T, et al. Individualised exercise improves endothelial function in patients with rheumatoid arthritis. Ann Rheum Dis 2014;73:748–51.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 7.

    Radice A, Bianchi L, Sinico RA. Anti-neutrophil cytoplasmic autoantibodies: methodological aspects and clinical significance in systemic vasculitis. Autoimmun Rev 2013;12:487–95.Web of SciencePubMedCrossrefGoogle Scholar

  • 8.

    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.PubMedCrossrefGoogle Scholar

  • 9.

    Hagen EC, Daha MR, Hermans J, Andrassy K, Csernok E, Gaskin G, et al. Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization. Kidney Int 1998;53:743–53.CrossrefPubMedGoogle Scholar

  • 10.

    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.Web of ScienceCrossrefGoogle Scholar

  • 11.

    Bossuyt X, Cohen Tervaert JW, Arimura Y, Blockmans D, Flores-Suarez LF, Guillevin L, et al. Position paper: revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol 2017;13:683–92.CrossrefPubMedGoogle Scholar

  • 12.

    Haviv Y, Shovman O, Bragazzi NL, Sharif K, Yavne Y, Shoenfeld Y, et al. Patients with vasculitides admitted to the intensive care unit: implications from a single-center retrospective study. J Intensive Care Med 2017:885066617717223. [Epub ahead of print].PubMedGoogle Scholar

  • 13.

    Comarmond C, Crestani B, Tazi A, Hervier B, Adam-Marchand S, Nunes H, et al. Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature. Medicine (Baltimore) 2014;93:340–9.Web of SciencePubMedCrossrefGoogle Scholar

  • 14.

    Sinico RA, Radice A. Antineutrophil cytoplasmic antibodies (ANCA) testing: detection methods and clinical application. Clin Exp Rheumatol 2014;32(3 Suppl 82):S112–7.PubMedGoogle Scholar

  • 15.

    Csernok E, Ahlquist D, Ullrich S, Gross WL. A critical evaluation of commercial immunoassays for antineutrophil cytoplasmic antibodies directed against proteinase 3 and myeloperoxidase in Wegener’s granulomatosis and microscopic polyangiitis. Rheumatology (Oxford) 2002;41:1313–7.CrossrefPubMedGoogle Scholar

  • 16.

    Csernok E, Holle J, Hellmich B, Willem J, Tervaert C, Kallenberg CG, 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.PubMedGoogle Scholar

  • 17.

    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.PubMedGoogle Scholar

  • 18.

    Knight A, Ekbom A, Brandt L, Askling J. What is the significance in routine care of c-ANCA/PR3-ANCA in the absence of systemic vasculitis? A case series. Clin Exp Rheumatol 2008;26(3 Suppl 49):S53–6.PubMedGoogle Scholar

  • 19.

    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 Crohns Colitis 2008;2:1–23.CrossrefWeb of SciencePubMedGoogle Scholar

  • 20.

    Holle JU, Hellmich B, Backes M, Gross WL, Csernok E. Variations in performance characteristics of commercial enzyme immunoassay kits for detection of antineutrophil cytoplasmic antibodies: what is the optimal cut off? Ann Rheum Dis 2005;64:1773–9.CrossrefPubMedGoogle Scholar

  • 21.

    Bossuyt X, Rasmussen N, van Paassen P, Hellmich B, Baslund B, Vermeersch P, et al. A multicentre study to improve clinical interpretation of proteinase-3 and myeloperoxidase anti-neutrophil cytoplasmic antibodies. Rheumatology (Oxford) 2017;56:1533–41.PubMedCrossrefGoogle Scholar

  • 22.

    Lee KH, Kronbichler A, Park DD, Park Y, Moon H, Kim H, et al. Neutrophil extracellular traps (NETs) in autoimmune diseases: a comprehensive review. Autoimmun Rev 2017;16:1160–73.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 23.

    Jennette JC, Falk RJ, Hu P, Xiao H. Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Annu Rev Pathol 2013;8:139–60.PubMedCrossrefGoogle Scholar

  • 24.

    Nakazawa D, Tomaru U, Yamamoto C, Jodo S, Ishizu A. Abundant neutrophil extracellular traps in thrombus of patient with microscopic polyangiitis. Front Immunol 2012;3:333.Web of SciencePubMedGoogle Scholar

  • 25.

    Little MA, Al-Ani B, Ren S, Al-Nuaimi H, Leite M, Jr., Alpers CE, et al. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PLoS One 2012;7:e28626.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 26.

    Schönermarck U, Csernok E, Gross WL. Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis: challenges and solutions 2014. Nephrol Dial Transplant 2015;30(suppl_1):i46–52.Web of SciencePubMedGoogle Scholar

About the article

Corresponding author: Prof. Yehuda Shoenfeld, MD, FRCP, MACR, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer 5265601, Israel, Phone: +(972-3) 530-8070


Received: 2017-11-12

Accepted: 2017-12-28

Published Online: 2018-01-29

Published in Print: 2018-05-24


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

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 6, Pages 947–953, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-1053.

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