Background/Purpose: In 2017, the multicenter European Vasculitis Study Group (EUVAS) evaluated the diagnostic accuracy of a wide spectrum of detection tests of MPO and PR3-ANCAs (Ann Rheum Dis 2017;76:647). The study reported a high diagnostic performance of PR3-ANCA and MPO-ANCA by antigen-specific immunoassay to discriminate ANCA-associated vasculitis (AAV) from disease controls. They concluded that dual indirect immunofluorescence (IIF) /antigen-specific immunoassay testing of each sample is not necessary for maximal diagnostic accuracy and proposed that the current international consensus on ANCA testing for AAV needs revision. However, the AAV patients of the EUVAS study were predominantly PR3-ANCA positive. The epidemiological manifestations of AAV differ geographically. We aimed to compare various ANCA detection methods in predominantly MPO ANCA-associated vasculitis cohort.

Methods: Stored sera (obtained at the time of diagnosis) from 162 patients with newly diagnosed and untreated AAV, including microscopic polyangiitis (MPA; n = 115), granulomatosis with polyangiitis (GPA; n = 32), and eosinophilic granulomatosis with polyangiitis (EGPA; n = 7), from 124 disease controls, and from 50 unmatched healthy controls were tested for the presence of perinuclear and cytoplasmic pattern ANCA (P-ANCA and C-ANCA, respectively) by standard IIF, and for the presence of MPO-ANCA and PR3-ANCA by 4 different antigen-specific immunoassays: an enzyme-linked immunosorbent assay (ELISA), a chemiluminescent enzyme immunoassay (CLEIA), a third-generation fluorescent enzyme immunoassay (FEIA), and a latex agglutination turbidimetry (LA). Patients with AAV were defined and classified according to the European Medicines Agency algorithm. Patients in whom inflammatory bowel disease and/or autoimmune liver disease was considered were excluded. Sensitivities and specificities for AAV diagnoses and concordance of each AAV tests were evaluated.

Results: P-ANCA and MPO-ANCA was detected in 82% and 61–82% of the AAV patients, respectively. C-ANCA and PR3-ANCA was detected in 8% and 6–11% of the AAV patients, respectively. When P and C-ANCAs or MPO and PR3-ANCAs were combined, the sensitivities and specificities for AAV diagnoses were 90% and 94% with the IIF, 82% and 98% with the ELISA, 89% and 95% with the CLIA, 88% and 97% with the FEIA, and 65% and 91% with the LA, respectively. Κ coefficients between P-ANCA and MPO-ANCA (by the ELISA, CLIA, FEIA, and LA) were 0.87, 0.96, 0.93, and 0.64, respectively. Κ coefficients between C-ANCA and PR3-ANCA (by the ELISA, CLIA, FEIA, and LA) were 0.54, 0.59, 0.58, and 0.48, respectively. Screening for ANCA with the CLIA and FEIA and confirming by IIF strategy increased the diagnostic accuracy only minimally (from 0.92 to 0.93 with CLIA/IIF and from 0.93 to 0.94 with FEIA/IIF).

Conclusion: The present study demonstrated a high diagnostic performance by antigen-specific immunoassays to discriminate AAV from controls in predominantly MPO-ANCA-associated vasculitis cohort. Consequently, increase in overall performance by dual IIF/antigen-specific immunoassay testing of each sample in such cohort is minimal.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-various-anca-detection-methods-in-predominantly-mpo-anca-associated-vasculitis-cohort/