Antigen-specific ANCA ELISAs have different sensitivities for active and treated vasculitis and for nonvasculitic disease.

This study evaluated the performance of 12 assays for antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) and myeloperoxidase (MPO) in 55 active and 68 treated cases of vasculitis and in nonvasculitic disease. It examined within- and between-assay precision; binding curves, binding levels, and interassay consistency; and sensitivity, specificity, and receiver operating characteristic analysis. All assays were highly sensitive for active vasculitis (median, 94%; range, 91%-96%), but sensitivities were more varied in treated disease (median, 69%; range, 57%-82%). Binding curves and binding levels were also very variable in PR3-ANCA and MPO-ANCA assays. This has implications for studies correlating ANCA levels with disease activity and in developing ANCA-based treatment guidelines. PR3-ANCA and MPO-ANCA assays need to be standardized as a matter of urgency, but in the meantime, individual laboratories must understand the limitations of the assays used, especially with low-level ANCA in treated vasculitis and nonvasculitic disease. Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against antigens in the cytoplasmic granules of neutrophils and monocytes. 1,2 The detection of these antibodies is important in the early diagnosis of systemic small vessel vasculitis 2,3 because many patients with untreated Wegener granulomatosis (WG) reach end-stage kidney disease or die within 2 years, and kidney failure often develops in patients with untreated microscopic polyangiitis (MPA). Mortality and morbidity remain high, even with current treatment regimens and renal transplantation. 4