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Diagnostic significance of ANCA in vasculitis

Nature Clinical Practice Rheumatology volume 2, pages 174–175 (2006)Cite this article

Wegener's granulomatosis, microscopic polyangiitis (MPA), Churg–Strauss syndrome, and primary pauci-immune crescentic glomerulonephritis are associated with circulating anti-neutrophil cytoplasmic autoantibodies (ANCA), and are collectively called ANCA-associated vasculitides (AAV). Only two types of ANCA—one with cytoplasmic fluorescence pattern (C-ANCA) and specificity for proteinase 3 (PR3-ANCA), and the other with perinuclear fluorescence pattern (P-ANCA) with myeloperoxidase specificity (MPO-ANCA)—account for this association and both are highly specific markers for these vasculitides. These autoantibodies have been the subject of intensive studies and a growing body of evidence has been found supporting a specific role of ANCA in the pathogenesis of AAV. The widespread use of ANCA screening has resulted in increased numbers of false-positive results, leading to greater difficulty in test interpretation. Therefore, a rational strategy for ANCA testing is needed.

The early literature on the clinical utility of ANCA as a diagnostic marker for Wegener's granulomatosis has been evaluated in a meta-analysis by Rao and colleagues:1 the sensitivity of C-ANCA testing for Wegener's granulomatosis ranged from 34 to 92%, and the specificity ranged from 88 to 100%. Several new, retrospective studies have reported wide ranging sensitivities and specificities of ANCA tests, depending not only on the characteristics of the assays used, but also on the patient population included in each study. It has been shown that 60–95% of all ANCA found in patients with Wegener's granulomatosis are C-ANCA and PR3-ANCA. The value of ANCA testing rises when a combined procedure is used:2the results of the immunofluorescence test for ANCA detection can be greatly increased by the addition of a well-standardized, antigen-specific enzyme-linked immunosorbent assay (ELISA). When the results of the immunofluorescence tests were combined with those of the ELISA (C-ANCA/PR3-ANCA and P-ANCA/MPO-ANCA), the diagnostic specificity increased to 99%. The test sensitivity of the combination of C-ANCA/PR3-ANCA and P-ANCA/MPO-ANCA for Wegener's granulomatosis, MPA or primary pauci-immune crescentic glomerulonephritis was 73%, 67% and 82%, respectively.2 The sensitivity of C-ANCA/PR3-ANCA tests for Wegener's granulomatosis is related to the extent, severity, and activity of the disease at the time of sampling. The association of MPA with P-ANCA/MPO-ANCA is reported to be in the range of 40–80%.2 Few patients with Wegener's granulomatosis are P-ANCA/MPO-ANCA-positive and few patients with MPA are C-ANCA/PR3-ANCA-positive. ANCA have been detected with variable frequency (10–70%) in Churg–Strauss syndrome; both PR3 and MPO have been described as target antigens. In general, ANCA levels are usually high at presentation and ANCA testing can been used to monitor disease activity and to differentiate disease flares from basal illness.3

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Authors and Affiliations

  1. senior research scientist at the Department of Rheumatology, University Hospital of Schleswig-Holstein,

    Elena Csernok, Peter Lamprecht & Wolfgang L Gross

  2. Professor of Rheumatology at the Rheumaklinik Bad Bramstedt,

    Elena Csernok, Peter Lamprecht & Wolfgang L Gross

  3. Professor in the Department of Rheumatology at the University Hospital of Schleswig-Holstein in Lübeck, Germany

    Elena Csernok, Peter Lamprecht & Wolfgang L Gross

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  1. Elena Csernok
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Correspondence to Wolfgang L Gross.

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Csernok, E., Lamprecht, P. & Gross, W. Diagnostic significance of ANCA in vasculitis. Nat Rev Rheumatol 2, 174–175 (2006). https://doi.org/10.1038/ncprheum0159

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