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Anti-neutrophil cytoplasmic autoantibodies: methodological aspects and clinical significance in systemic vasculitis.

Abstract
Antineutrophil cytoplasmic antibodies (ANCA) are the serological hallmark of some idiopathic systemic vasculitides, such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and, to a lesser extent, Churg-Strauss syndrome (CCS), the so-called ANCA-associated vasculitides (AAV). ANCA were first detected by immunofluorescence (IIFT), subsequently the target antigens myeloperoxidase (MPO) and proteinase 3 (PR3) were identified, allowing the development of the quantitative, antigen-specific assays. According to the guidelines, combining IIFT and PR3-ANCA/MPO-ANCA assures the optimal diagnostic specificity. Antigen specificity does not effectively differentiate among the different AAV, however C-ANCA/PR3-ANCA are mainly found in GPA, while P-ANCA/MPO-ANCA are more prevalent in MPA and CSS. Despite their diagnostic value, the performance of the widespread immunometric assays for ANCA testing is disappointing, particularly for the low sensitivity. In recent years, more "sensitive" assays have been developed, using the microplate as well as fully the automated technologies, with promising preliminary results. ANCA, may be detected in a number of pathological conditions other than small vessel vasculitis. However, in most of these non-vasculitic patients ANCA do not recognize MPO or PR3 as target antigens, but other granulocyte components, often multiple or unknown specificities. A positive ANCA result by itself is not diagnostic for AAV, clinical evidence and possibly histological confirmation are always required. On the other hand, a negative test result cannot completely rule out a diagnosis of AAV, as AAV without detectable ANCA exist. The appropriate use of ANCA testing strongly improves the diagnostic accuracy and clinical usefulness of the results.
AuthorsAntonella Radice, Laura Bianchi, Renato Alberto Sinico
JournalAutoimmunity reviews (Autoimmun Rev) Vol. 12 Issue 4 Pg. 487-95 (Feb 2013) ISSN: 1873-0183 [Electronic] Netherlands
PMID22921790 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2012. Published by Elsevier B.V.
Chemical References
  • Antibodies, Antineutrophil Cytoplasmic
  • Epitopes
  • Peroxidase
  • Myeloblastin
Topics
  • Antibodies, Antineutrophil Cytoplasmic (immunology)
  • Epitopes (immunology)
  • Humans
  • Immunoassay (methods, standards)
  • Myeloblastin (immunology)
  • Peroxidase (immunology)
  • Systemic Vasculitis (diagnosis, immunology)

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