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Revised 2017 international consensus on ANCA testing in small vessel vasculitis: support from an external quality assessment
  1. Sylvia Broeders1,
  2. Sylvie Goletti2,
  3. Jean-Paul Tomasi2,
  4. Carolien Bonroy3,
  5. René-Louis Humbel4,
  6. Laurence Lutteri5,
  7. Sofie Schouwers6,
  8. Lieve Van Hoovels7,
  9. Martine Vercammen8,
  10. Xavier Bossuyt9
  1. 1 Quality of Laboratories, Sciensano, Brussels, Belgium
  2. 2 Cliniques Universitaires Saint-Luc, Brussels, Belgium
  3. 3 Laboratory Medicine, University Hospitals Gent, Ghent, Belgium
  4. 4 BioneXt Lab Leudelange, Grand Duchy of Luxembourg, Leudelange, Luxembourg
  5. 5 Department of Clinical Chemistry, University Hospital of Liège, Liège, Belgium
  6. 6 Laboratory Medicine, GasthuisZusters Antwerp, Antwerp, Belgium
  7. 7 Laboratory Medicine, OLVZ Aalst, Aalst, Belgium
  8. 8 Martine Vercammen, Laboratory Medicine, AZ Sint-Jan Brugge, Brugge, Belgium
  9. 9 Laboratory Medicine, University Hospitals Leuven and Department of Microbiology and Immunology, Leuven, Belgium
  1. Correspondence to Dr Xavier Bossuyt, Laboratory Medicine, University Hospitals Gasthuisberg, Herestraat 49, Leuven 3000, Belgium; xavier.bossuyt{at}uzleuven.be

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We read with great interest the multicentre study of Damoiseaux et al 1–3 on the detection of antineutrophil cytoplasmic antibodies (ANCA). ANCAs are important laboratory markers to support the diagnosis of ANCA-associated small vessel vasculitis (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Traditionally, laboratories screen for ANCA by indirect immunofluorescence (IIF) and IIF positive samples are further evaluated for antibodies to proteinase 3 (PR3) or myeloperoxidase (MPO) by specific immunoassays. Such diagnostic algorithm is based on an international consensus statement on ANCA testing issued in 1999.4 Over the last two decades, the diagnostic performance of immunoassays has significantly improved. The recent multicentre study showed a high diagnostic performance of PR3-ANCA and MPO-ANCA by immunoassay and a large variability between IIF methods.1 5 Accordingly, a 2017 revision of the international consensus on ANCA testing in GPA and MPA concluded that ‘high-quality immunoassays can be used as the primary screening method for patients suspected of having the ANCA-associated vasculitides GPA and MPA without the categorical need for IIF.6 The study that formed the basis for the 2017 revision of the consensus was retrospective and performed in specialised laboratories.1 5 We here report the results of a recent external quality assessment on ANCA. Such programme assesses the real-life performance in clinical laboratories nationwide.

A sample containing MPO-ANCA was distributed to 90 Belgian laboratories. The sample was obtained from a 66-year-old woman hospitalised for a rapidly progressive glomerulonephritis (MPO-ANCA positive) and with a suspicion of alveolar haemorrhage. Seventy-seven laboratories performed IIF, 83 immunoassay and 70 both IIF and immunoassay. Of the 77 laboratories that performed IIF, 71 (92.2%) reported P-ANCA, 1 (1.3%) C-ANCA, 1 (1.3%) atypical ANCA, 2 (2.6%) ANCA positive and 2 (2.6%) ANCA negative. Fifty-three laboratories reported an IIF titre, which varied from 1/10 to 1/640. Table 1 gives an overview of the IIF results. Of the 83 laboratories that performed an immunoassay, all found MPO-ANCA. An overview of the immunoassays used is given in table 2. Fluoroenzyme immunoassay was the most frequently used (n=48) immunoassay, with a mean value of 62.0 U/mL (SD: 8.3 U/mL). Such value is associated with a likelihood ratio of 59 (95% CI 30 to 113.5) for AAV.7

Table 1

IIF results of 77 Belgian laboratories for an external quality control sample containing MPO-ANCA. Fifty-three laboratories performed a titration

Table 2

Overview of immunoassays for ANCA determination in Belgian laboratories

In conclusion, a Belgian external quality assessment scheme for MPO-ANCA revealed variability between IIF results and a lower sensitivity of IIF than of immunoassay. Therefore, these results corroborate the revised 2017 international consensus for ANCA testing in GPA and MPA that states immunoassay is the preferred method to detect ANCA for diagnosis of GPA and MPA.

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Footnotes

  • Contributors SB organised the study, analysed the data and summarised the results. SG and JPT provide the patient sample. SB, SG, JPT, CB, RLH, LL, MV, SS, LVH and XB discussed the data and revised the manuscript. XB wrote the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests XB has been a consultant to Inova Diagnostics and to Thermo Fisher.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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