Potential Interference by Antineutrophil Cytoplasmic Autoantibodies in Myeloperoxidase Immunoassays

Abstract

Myeloperoxidase (MPO)1 has been identified as a potential marker of cardiovascular disease (1). As the clinical utility of new biomarkers is identified and commercial assays are developed, limitations on their use need to be identified and reported. Antineutrophil cytoplasmic autoantibodies (ANCAs) are known to exist in patients with diseases characterized by primary systematic vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, and Churg– Strauss syndrome, and in those with idiopathic pauci-immune necrotizing crescentic glomerulonephritis, systemic lupus erythematosus, and rheumatoid arthritis (2). In particular, the immunofluorescence- staining pattern for perinuclear ANCAs (pANCAs) is associated with anti-MPO autoantibodies. pANCAs are most prevalent in microscopic polyangiitis (40%–80%), followed by Churg–Strauss syndrome (20%–30%) and Wegener granulomatosis (5%–20%). Autoantibodies can interfere with assays when the autoantibodies bind to analyte epitopes that are similar to those of the monoclonal antibodies used in the immunoassay. Anti-MPO autoantibodies are likely to bind to MPO in the sample and block or partially mask the epitopes necessary for binding to the antibodies used to capture and detect MPO. We evaluated the effect of MPO autoantibodies on the performance of the Cardio MPO™ immunoassay (PrognostiX), which has been cleared by the US Food and Drug Administration. We similarly evaluated an immunoassay under development for the Abbott ARCHITECT® instrument (Abbott …