Distinct differences in autoantigen specificity of anti-neutrophil cytoplasm antibodies in systemic vasculitides and other inflammatory diseases

Background: Anti-neutrophil cytoplasm antibodies in necrotizing vasculitide s need to be distinguished from ANCAs(1) in other inflammatory conditions t o avoid clinical misinterpretation. Objectives: To help clinicians and laboratory scientists recognize and util ize vasculitis-related ANCAs as an aid in diagnostic workup and patient fol low-up, and be aware that ANCAs with different characteristics are commonly found in other chronic inflammatory conditions that persistently engage ne utrophils in the inflammatory process. Methods: Indirect immunofluorescence and enzyme immunoassay methods were us ed to detect ANCAs with both known and unknown neutrophil autoantigenic tar gets. Results: Primary necrotizing small vessel vasculitides such as Wegener's gr anulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and renal-l imited rapidly progressive necrotizing glomerulonephritis target either the serine protease proteinase 3 or myeloperoxidase in azurophilic granules. I n ulcerative colitis and rheumatoid arthritis, we found multiple ANCA targe ts contained in azurophilic and specific granules, the cytosol and the nucl eus, whereas PR3(2) and MPO3 were not, or only weakly, recognized. Conclusions: ANCAs typically found in active SVV4 are demonstrable both by indirect immunofluorescence and antigen-specific enzyme immunoassay, and st rong reactivity to either PR3 or MPO is characteristic. Strong ANCA with MP O reactivity is also found in some patients with drug-induced syndromes (lu pus, vasculitis). Intermediate to strong perinuclear ANCAs are found in a s ubstantial proportion of patients with UC5 (40-60%) and RA(6) (30-70%), but in these conditions the ANCAs have many antigen targets that are only weak ly recognized.