Antineutrophil cytoplasmic antibodies in rheumatoid arthritis. Characterization and clinical correlations.

Abstract

To study the prevalence, interrelationships, and target antigens of antineutrophil cytoplasmic antibodies (ANCA) in rheumatoid arthritis (RA) and to relate their presence to disease duration and to the occurrence of extraarticular manifestations, including vasculitis. Sera from 94 patients with RA (31 with recent-onset disease, 35 with longstanding disease but without extraarticular manifestations, and 28 with extraarticular disease) were studied for the presence of ANCA by indirect immunofluorescence. All sera were tested by enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to proteinase 3, myeloperoxidase (MPO), elastase, lactoferrin (LF), and cathepsin G (CG), and by Western blotting for antibodies to neutrophil proteins. Seventy percent of the 94 sera showed staining of the nuclei of ethanol-fixed neutrophils; 32% of the 94 were proven to have ANCA, as manifested by their cytoplasmic staining pattern on paraformaldehyde-fixed neutrophils. In the ELISA, 19 sera reacted with LF, 1 with MPO, and 1 with CG. By Western blotting, 21 sera reacted with LF, and 15 reacted with previously unknown polypeptides (7 sera with a 67/66-kd doublet and 8 with a 63/54-kd doublet). Neither of these antibodies was associated with a particular subset of the disease, but the prevalence of the antibodies tended to increase among patients with longstanding disease. ANCA in RA patients are directed toward diverse cytoplasmic antigens of the neutrophil, in particular, LF and other, not yet fully characterized polypeptides. The antibodies are not a marker for a disease subset, but are probably a corollary of chronic inflammation.