DIAGNOSTIC-VALUE OF STANDARDIZED ASSAYS FOR ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN IDIOPATHIC SYSTEMIC VASCULITIS

Anti-neutrophil cytoplasmic antibodies (ANCA) are widely used as diagn ostic markers for Wegener's granulomatosis (WG), microscopic polyangii tis (MPA), Churg Strauss syndrome (CSS) and idiopathic rapidly progres sive glomerulonephritis (iRPGN). The objective of this study was to ev aluate the diagnostic value of ANCA measurement by the indirect immuno fluorescence (IIF) test, and by anti-PR3 and anti-MPO ELISA performed in different locations, in patients with idiopathic small vessel vascu litis. Fourteen centers participated in a standardization study of ANC A assays, and entered a total number of 169 newly diagnosed and 189 hi storical patients with idiopathic systemic vasculitis or iRPGN. Patien ts were classified according to a pre-defined diagnostic classificatio n system. Results were compared with those of 184 disease controls and 740 healthy controls. The IIF test was performed according to standar d methodology; ELISAs had been standardized among the participants in a previous phase of the study. The sensitivities of assays in patients were as follows. The sensitivity in WG was: cANCA 64%, pANCA 21%, ant i-PR3 66%, anti-MPG 24%. In MPA the sensitivity was: cANCA 23%, pANCA 58%, anti-PR3 26%, anti-MPG 58%. Sensitivity in iRPGN was: cANCA 36%, pANCA 45%, anti-PR3 50%, anti-MPO 64%. The specificity of assays (rela ted to disease controls) was: cANCA 95%, pANCA 81%, anti-PR3 87%, anti -MPO 91%. When the results of the IIF test were combined with those of the ELISAs (cANCA/anti-PR3 positive, pANCA/anti-MPO positive), the di agnostic specificity increased to 99%. The sensitivity of the combinat ion of cANCA + anti-PR3 or pANCA + anti-MPO for WG, MPA or iRPGN was 7 3%, 67% and 82%, respectively. From this study we conclude that the va lue of the IIF test for ANCA detection can be greatly increased by the addition of a well standardized antigen-specific ELISA. In a signific ant number of patients with idiopathic small vessel vasculitis, howeve r, the ANCA test results (either in IIF or ELISA) are negative.