Test characteristics of immunofluorescence and ELISA tests in 856 consecutive patients with possible ANCA-associated conditions

Objective. To examine the test characteristics of immunofluorescence (IF) a nd enzyme-linked immunosorbent assays (ELISA) in a consecutive series of pa tients under evaluation for anti-neutrophil cytoplasmic antibody (ANCA)-ass ociated vasculitis (AAV). Methods. Using stored sera, we performed a cross-sectional study on 856 con secutive patients tested prospectively for ANCA by IF. Based on guidelines from the 1994 Chapel Hill Consensus Conference (CHCC), rye determined each patient's underlying diagnosis by a medical records review without regard t o their ANCA status the CHCC guidelines do not require ANCA as a prerequisi te for diagnosis). We grouped patients with forms of vasculitis commonly as sociated with ANCA into one of 4 types of AAV: Wegener's granulomatosis (n = 45), microscopic polyangiitis (n = 12), Churg-Strauss syndrome (n = 4), a nd pauci-immune glomerulonephritis (n = 8). We also classified patients wit hout clinical evidence of AAV (92 % of all patients tested) into 5 predefin ed categories of disease (including "other") and an additional category for no identifiable disease. In a blinded fashion, we then performed ELISAs on the stored serum for antibodies to proteinase-3 (PR3) and myeloperoxidase (MPO) and calculated the test characteristics for both ANCA assay technique s. Results. Sixty-nine of the 856 patients (8.1 %) had clinical diagnoses of A AV based on CHCC guidelines. The positive predictive value (PPV) of ELISA f or AAV was superior to that of IF, 83% versus 45%. For patients with both p ositive IF tests and positive ELISA tests, the PPV increased to 88%. Both I F and ELISA had high negative predictive values 97% and 96%, respectively). Positive ELISA tests were associated with higher likelihood ratios (LR) th an IF (54.2 [95% CI = 26.3, 111.5] versus 9.4 [95% CI = 6.9, 12.7]). The LR of both a positive IF and a positive ELISA was 82.1 95% CI = 33.3, 202.5). Conclusions. Compared with IF, an ELISA test for ANCA was associated with a substantially higher PPV and LR for AAV. This fact, combined with the grea ter sensitivity of IF, suggests that an effective testing strategy is to pe rform ELISA tests only on samples that are positive for ANCA by IF.