ABSTRACT
Antineutrophil cytoplasmic antibodies (ANCA) have recently been described in association with necrotizing glomerulonephritis, systemic vasculitis, and other autoimmune-mediated connective tissue diseases, including systemic lupus erythematosus (SLE) and polychondritis. At least two distinct classes of ANCA have been described, differentiated by characteristic immunofluorescence patterns using neutrophils as substrate for indirect immunofluorescence assay (IFA). A focal, centrally accentuated, finely granular cytoplasmic staining pattern (c-ANCA) is both sensitive and specific for Wegener's granulomatosis (WG) and is thus a useful clinical adjunct in the diagnosis and monitoring of disease activity in WG. The second class of ANCA, defined by a perinuclear immunofluorescent staining pattern (p-ANCA) on standardized IFA, has not been studied as extensively. It appears to occur in a variety of connective tissue diseases, most often necrotizing glomerulonephritis other than WG, systemic vasculitis with renal involvement, and SLE. In screening more than 2000 serum samples received in our rheumatology laboratory for ANA testing, we found p-ANCA in 10 patients. All 10 had evidence of systemic autoimmune disease, though with wide variation in extent and severity of disease. All 10 had other autoantibodies, most frequently ANA (60%). Our studies suggest that p-ANCA define a heterogeneous patient population with a spectrum of autoimmune disease, most frequently necrotizing glomerulonephritis and systemic vasculitis. Future studies will establish the role of p-ANCA in clinical medicine and broaden our understanding of the origin and possible pathogenesis of ANCA and autoantibodies in general.
