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Twenty-eight years with antineutrophil cytoplasmic antibodies (ANCA): how to test for ANCA — evidence-based immunology?

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Abstract

Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and primary pauci-immune crescentic glomerulonephritis are associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA) (collectively called ANCA-associated vasculitides, AAV). Two types of ANCA, one with a cytoplasmic fluorescence pattern (C-ANCA) and specificity for proteinase 3 (PR3-ANCA) and the other with a perinuclear pattern (P-ANCA) and specificity for myeloperoxidase (MPO-ANCA), account for this association and are highly specific markers for these vasculitides. AAV most often require therapy with cytotoxic and antiinflammatory agents, and hence a well-established diagnosis is mandatory to avoid unnecessary and risky treatment. The widespread use of ANCA screening in the past decade has resulted in the occurrence of greater numbers of false-positive results and has led to greater difficulty in test interpretation. Methods for ANCA detection have been standardized internationally in large multicentre studies and an international consensus statement on testing and reporting of ANCA has been pub lished (1999 and 2003). Despite these advances, problems with the extended use of ANCA testing in daily clinical practice remain. They may be summarized as follows: (1) the basic standards for ANCA testing are not uniformly met; (2) there is still controversy over the value of formalin fixation of neutrophils in differentiating P-ANCA from antinuclear antibodies (what is the place of this substrate in ANCA testing?); (3) the new generation of PR3-ANCA and MPO-ANCA ELISAs are more sensitive and specific than immunofluorescence testing (should ELISAs replace the immunofluorescence test?); and (4) should alternative methods for ANCA detection such as image analysis and/or multiplex immunoassays be used for screening? In this paper, we review these issues, identify areas of uncertainty, and provide practical guidelines where possible.

References

  1. 1.

    Csernok E, Lamprecht P, Gross WL (2006) Diagnostic significance of ANCA in vasculitis. Nat Clin Pract Rheumatol 2:174–175

  2. 2.

    Rao JK, Weinberger M, Oddone EZ et al (1995) The role of antineutrophil cytoplasmic antibody (C-ANCA) testing in the diagnosis of Wegener granulomatosis. A literature review and metaanalysis. Ann Intern Med 123:925–932

  3. 3.

    Hagen EC, Daha MR, Hermans J et al (1998) Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization. Kidney Int 53:743–753

  4. 4.

    Kain R, Exner M, Brandes R et al (2008) Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med 14:1088–1096

  5. 5.

    Savige J, Gillis D, Benson E et al (1999) International Consensus Statement on Testing and Reporting of Antineutrophil Cytoplasmic Antibodies (ANCA). Am J Clin Pathol 111:507–513

  6. 6.

    Csernok E, Holle J, Hellmich B et al (2004) Evaluation of capture ELISA for detection of neutrophil cytoplasmic antibodies directed against proteinase 3 in Wegener’s granulomatosis: first results from a multicentre study. Rheumatology (Oxford) 43:174–180

  7. 7.

    Pollock W, Trevisin M, Savige J (2008) Testing on formalin-fixed neutrophils is less sensitive and specific for small vessel vasculitis, and less sensitive for MPO-ANCA, than most ELISAs. J Immunol Methods 339:141–145

  8. 8.

    Holle JU, Hellmich B, Backes M et al (2005) Variations in performance characteristics of commercial enzyme immunoassay kits for the detection of antineutrophil cytoplasmic antibodies: what is the optimal cut-off? Ann Rheum Dis 64:1773–1779

  9. 9.

    Hellmich B, Csernok E, Fredenhagen G et al (2007) A novel high sensitivity ELISA for detection of antineutrophil cytoplasm antibodies against proteinase-3. Clin Exp Rheumatol 25:1–5

  10. 10.

    Holle JU, Csernok E, Fredenhagen G et al (2010) Clinical evaluation of hsPR3-ANCA ELISA for detection of ANCA. Ann Rheum Dis 69:468–469

  11. 11.

    Boomsma MM, Damoiseaux FG, Stegeman CA et al (2003) Image analysis: a novel approach for the quantification of ANCA levels in patients with Wegener’s granulomatosis. J Immunol Methods 274:27–35

  12. 12.

    Trevisin M, Pollock W, Savige J (2008) Evaluation of a multiplex flow cytometric immunoassay to detect PR3- and MPO-ANCA in active and treated vasculitis, and in inflammatory bowel disease. J Immunol Methods 336:104–112

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Correspondence to Elena Csernok.

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Csernok, E., Holle, J.U. Twenty-eight years with antineutrophil cytoplasmic antibodies (ANCA): how to test for ANCA — evidence-based immunology?. Autoimmun Highlights 1, 39–43 (2010) doi:10.1007/s13317-010-0007-3

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Keywords

  • ANCA
  • Screening
  • Proteinase 3
  • Myeloperoxidase
  • ANCA-associated vasculitides