PREVALENCE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN A LARGE INCEPTION COHORT OF PATIENTS WITH CONNECTIVE-TISSUE DISEASE

Background: Two types of antineutrophil cytoplasmic antibodies (ANCA), antiproteinase 3 antibodies (anti-PR3) and antimyeloperoxidase antibo dies (anti-MPO), are useful in the diagnosis of such types of vasculit is as Wegener granulomatosis and microscopic polyangiitis. Connective tissue diseases frequently appear in the differential diagnosis of thi s spectrum of vasculitis. Objective: To determine the prevalence of AN CA in patients with connective tissue disease. Design: Blinded, contro lled study of a 5-year inception cohort. Setting: Tertiary-care univer sity teaching hospitals. Patients: 70 patients with rheumatoid arthrit is, 70 patients with systemic lupus erythematosus, 45 patients with sc leroderma, 36 patients with inflammatory myositis, 44 patients with th e Sjogren syndrome, 33 patients with the antiphospholipid syndrome, an d 165 patients with early undifferentiated connective tissue disease ( EUCTD). Serum was taken from 200 blood donors and 52 patients who had known vasculitis and positive results on tests for anti-PR3 or anti-MP O; these patients served as controls. Measurements: The presence of an ti-PR3 and anti-MPO was determined by combining the results of indirec t immunofluorescence tests for cytoplasmic (C-ANCA) and perinuclear (P -ANCA) patterns with the results of enzyme-linked immunosorbent assays (ELISAs) directed to measure antigen. Results: Cytoplasmic ANCA was n ot detected in any study or control patient. Perinuclear ANCA was comm only detected among patients with lupus (31%) but was uncommon among p atients in other groups (0% to 5%). In all cases, P-ANCA was associate d with the presence of antinuclear antibodies. Atypical ANCA immunoflu orescence patterns were fairly common in all groups (11% to 39%). Anti proteinase 3 was detected by ELISA in 9 study patients (1 patient with rheumatoid arthritis, 1 with lupus, 1 with polymyositis, and 6 with E UCTD). Antimyeloperoxidase was detected by ELISA in 2 study patients ( 1 with rheumatoid arthritis and 1 with lupus). None of the patients wi th positive ELISA results had evidence of renal vasculitis during foll ow-up. When an ANCA scoring system that combines immunofluorescence an d ELISA was used, the test specificity for vasculitis was 99.5% among patients with connective tissue disease. Conclusions: Patients with co nnective tissue disease are known to develop multiple autoantibodies; positivity for anti-PR3 and anti-MPO ANCA in such patients is rare. Cy toplasmic ANCA immunofluorescence is highly specific for anti-PR3. How ever, P-ANCA immunofluorescence, which may have positive results becau se of the presence of antinuclear antibodies, is not a specific marker of anti-MPO. A rigorous ANCA testing system that combines the results of immunofluorescence with those of ELISA is highly specific for Wege ner granulomatosis and related vasculitides even in patients with conn ective tissue disease.