Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis

Abstract

| Anti-neutrophil cytoplasmic antibodies (ANCAs) are valuable laboratory markers used for the diagnosis of well-defined types of small-vessel vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). According to the 1999 international consensus on ANCA testing, indirect immunofluorescence (IIF) should be used to screen for ANCAs, and samples containing ANCAs should then be tested by immunoassays for proteinase 3 (PR3)-ANCAs and myeloperoxidase (MPO)-ANCAs. The distinction between PR3-ANCAs and MPO-ANCAs has important clinical and pathogenic implications. As dependable immunoassays for PR3-ANCAs and MPO-ANCAs have become broadly available, there is increasing international agreement that high-quality immunoassays are the preferred screening method for the diagnosis of ANCA-associated vasculitis. The present Consensus Statement proposes that high-quality immunoassays can be used as the primary screening method for patients suspected of having the ANCA-associated vaculitides GPA and MPA without the categorical need for IIF, and presents and discusses evidence to support this recommendation.NATURE REVIEWS | RHEUMATOLOGY VOLUME 13 | NOVEMBER 2017 | 683 CONSENSUS STATEMENT © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .Given the improvements in antigen-specific immuno assays, the international consensus on the testing of ANCAs in small-vessel vasculitis seems in need of updating [7][8][9][10] . In this manuscript, a revised 2017 international consensus is proposed by a group of international experts (from North and Central America, Australia, Europe and Asia) in the ANCA field. This Consensus Statement highlights the value of ANCA testing as a tool for diagnosis (but not follow-up) of GPA and MPA and gives a historical perspective of ANCAs in small-vessel vasculitis. This Consensus Statement does not, however, present evidence-based guidelines or a meta-analysis. MethodsThis Consensus Statement was prepared by a group of experts from four European laboratories (X.B., J.D., N.R., J.W.C.T. and E.C.) in person and by correspondence. The draft was circulated to each contributor and modified, and the resulting document was distributed by e-mail to 16 experts from four continents, selected based on their expertise and knowledge in clinical and/or laboratory aspects of AAV. This revised document resulted in a second round of discussions and revisions. The final document was returned to all contributors for ratification.The Consensus Statement is based on the results of a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of IIF versus antigen-specific immunoassays for ANCA detection 6,11,12 . This study, which showed a large variability between different IIF methods and a good diagnostic performance of PR3-ANCA and MPO-ANCA immunoassays 6 , indicated that the 1999 international consensus on ANCA testing for AAV needed revision. When the consensus was put toget...

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“…However, high-quality MPO/PR3 specific immunoassays, which can perform at least at well as IIF, are now recommended alone for routine ANCA testing. 70,71 ANCA is a good adjunct to diagnosis in the presence of an ap- 72 and MPO/PR3 specific antibodies can occur in the context of infection or drug use. 71 A total of 6% of the normal population will have a positive cANCA/pANCA, 72 and AAV patients can be ANCA negative, particularly in EGPA and localised GPA.…”

Look granulomatosis with polyangiitis (GPA) straight in the face: missed opportunities leading to a delayed diagnosis

“…While the causal mechanisms for most of the cases with facial palsy remain elusive, the autoimmune pathogenesis of GPA has been also added to the list. The serologic hallmark of GPA is the presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) predominantly directed against the proteinase 3 (PR3) and myeloperoxidase (MPO) enzymes released by neutrophils and monocytes upon cell activation [9]. In the absence of systemic signs of vasculitis at onset, only ANCA positivity could have allowed us to make the diagnosis of GPA.…”

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“…While the presence of ANCA in serum is a telltale feature of AAV, significant controversy existed until now whether ANCA should be detected by immunofluorescence (IF), enzyme‐linked immunosorbent assay (ELISA) or both techniques. A recent international consensus report recommends that the present day sensitive assays for anti‐PR3 and anti‐MPO antibodies using ELISA are adequate for the detection of ANCA without the need for additional IF . A number of papers have assessed the relevance of ANCA to clinical outcomes in AAV.…”