PR3-ANCA: A Promising Biomarker in Primary Sclerosing Cholangitis (PSC)

Stinton, Laura M.; Bentow, Chelsea; Mähler, Michael; Norman, Gary L.; Eksteen, Bertus; Mason, Andrew L.; Kaplan, Gilaad G.; Lindkvist, Björn; Hirschfield, Gideon M.; Milkiewicz, Piotr; Cheung, Angela; Janssen, Harry L A; Fritzler, Marvin J.

doi:10.1371/journal.pone.0112877

Cited by 65 publications

(55 citation statements)

References 39 publications

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“…In the past few years, studies have also reported that sensitive immunoassays can detect PR3-ANCAs in patients with ulcerative colitis 50,92,93 and primary sclerosing cholangitis 94 .…”

Section: Contraindications and Considerationsmentioning

confidence: 99%

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

et al. 2017

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| 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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“…In the past few years, studies have also reported that sensitive immunoassays can detect PR3-ANCAs in patients with ulcerative colitis 50,92,93 and primary sclerosing cholangitis 94 .…”

Section: Contraindications and Considerationsmentioning

confidence: 99%

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

et al. 2017

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“…The presence of additional antibodies should be assessed in patients who are positive for one antibody. A previous report showed that when rats are injected with anti-GBM antibody to develop glomerulonephritis, glomerulonephritis was more severe in rats immunized with MPO-ANCA than those that received control serum [21]. These findings underlie the significance of the assessment of more than one antibody in these patients.…”

Section: Discussionmentioning

confidence: 89%

Renal-limited vasculitis with elevated levels of multiple antibodies

et al. 2017

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“…[31][32][33] Typically, these sera reveal a P-ANCA by IIF. From the questionnaires, it appears that a substantial number of laboratories do not differentiate between these disease entities and the same algorithm that is designed for the detection of ANCA in relation to AAV is applied.…”

Section: Pr3mentioning

confidence: 99%

Diagnostic ANCA algorithms in daily clinical practice: evidence, experience, and effectiveness

Avery

Bons

Paassen

et al. 2016

Lupus

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Detection of antineutrophil cytoplasmic antibodies (ANCA) for ANCA-associated vasculitides (AAV) is based on indirect immunofluorescence (IIF) on ethanol-fixed neutrophils and reactivity toward myeloperoxidase (MPO) and proteinase 3 (PR3). According to the international consensus for ANCA testing, presence of ANCA should at least be screened for by IIF and, if positive, followed by antigen-specific immunoassays. Optimally, all samples are analyzed by both IIF and quantitative antigen-specific immunoassays. Since the establishment of this consensus many new technologies have become available and this has challenged the positioning of IIF in the testing algorithm for AAV. In the current paper, we summarize the novelties in ANCA diagnostics and discuss the possible implications of these developments for the different ANCA algorithms that are currently applied in routine diagnostic laboratories. Possible consequences of replacing ANCA assays by novel methods are illustrated by our data obtained in daily clinical practice. Eventually, it is questioned if there is a need to change the consensus, and if so, whether IIF can be discarded completely, or be used as a confirmation assay instead of a screening assay. Both alternative options require that ANCA requests for AAV can be separated from ANCA requests for gastrointestinal autoimmune diseases. Lupus (2016) 25, 917-924.

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PR3-ANCA: A Promising Biomarker in Primary Sclerosing Cholangitis (PSC)

Cited by 65 publications

References 39 publications

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

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

Renal-limited vasculitis with elevated levels of multiple antibodies

Diagnostic ANCA algorithms in daily clinical practice: evidence, experience, and effectiveness

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