ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN RHEUMATOID-ARTHRITIS - CHARACTERIZATION AND CLINICAL CORRELATIONS

Objective. To study the prevalence, interrelationships, and target ant igens of antineutrophil cytoplasmic antibodies (ANCA) in rheumatoid ar thritis (RA) and to relate their presence to disease duration and to t he occurrence of extraarticular manifestations, including vasculitis. Methods. 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-l inked immunosorbent assay (ELISA) for the presence of antibodies to pr oteinase 3, myeloperoxidase (MPO), elastase, lactoferrin (LF), and cat hepsin G (CG), and by Western blotting for antibodies to neutrophil pr oteins. Results. Seventy percent of the 94 sera showed staining of the nuclei of ethanol-fixed neutrophils; 32% of the 94 were proven to hav e ANCA, as manifested by their cytoplasmic staining pattern on parafor maldehyde-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 antibo dies was associated with a particular subset of the disease, but the p revalence of the antibodies tended to increase among patients with lon gstanding disease. Conclusion. 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 n ot a marker for a disease subset, but are probably a corollary of chro nic inflammation.