Background: Anti-neutrophil cytoplasm antibodies in necrotizing vasculitides need to be distinguished from ANCAs1 in other inflammatory conditions to avoid clinical misinterpretation.
Objectives: To help clinicians and laboratory scientists recognize and utilize vasculitis-related ANCAs as an aid in diagnostic workup and patient follow-up, and be aware that ANCAs with different characteristics are commonly found in other chronic inflammatory conditions that persistently engage neutrophils in the inflammatory process.
Methods: Indirect immunofluorescence and enzyme immunoassay methods were used to detect ANCAs with both known and unknown neutrophil autoantigenic targets.
Results: Primary necrotizing small vessel vasculitides such as Wegener’s granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and renal-limited rapidly progressive necrotizing glomerulonephritis target either the serine protease proteinase 3 or myeloperoxidase in azurophilic granules. In ulcerative colitis and rheumatoid arthritis, we found multiple ANCA targets contained in azurophilic and specific granules, the cytosol and the nucleus, whereas PR32 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 strong reactivity to either PR3 or MPO is characteristic. Strong ANCA with MPO reactivity is also found in some patients with drug-induced syndromes (lupus, vasculitis). Intermediate to strong perinuclear ANCAs are found in a substantial proportion of patients with UC5 (40–60%) and RA6 (30–70%), but in these conditions the ANCAs have many antigen targets that are only weakly recognized.
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1 ANCA = anti-neutrophil cytoplasm antibody
2 PR3 = protease proteinase 3
3 MPO = myeloperoxidase
4 SVV = small vessel vasculitides
5 UC = ulcerative colitis
6 RA = rheumatoid arthritis