ANTIMYELOPEROXIDASE AUTOANTIBODIES IN PATIENTS WITH NECROTIZING GLOMERULAR AND ALVEOLAR CAPILLARITIS

We conducted a prospective study of 651 Mediterranean patients from Catalonia (Spain) with well-defined forms of systemic vasculitis, connective tissue diseases, and renal and pulmonary disorders to determine the prevalence and clinical value of antineutrophil cytoplasmic autoantibodies (ANCA) with myeloperoxidase (MPO) specificity (MPOANCA). ANCA were first tested by indirect immunofluorescence on ethanol-fixed neutrophils. When a positive result was obtained, then MPO-ANCA were identified by performing the immunofluorescence assay again on neutrophils from a voluntary donor known to have a complete and selective deficiency of MPO. This disorder was detected by automated flow cytochemistry with the Technicon system and was further verified by cytochemical and biochemical studies. We detected MPO-ANCA in 61 of 70 (87%) patients with a perinuclear pattern (p-ANCA), but in none of 25 with a cytoplasmic pattern (c-ANCA). These results were corroborated by enzyme-linked immunosorbent assay (ELISA) using human purified MPO as a substrate. On immunofluorescence microscopy, all patients with MPO-ANCA were found to have a typical and restrictive immunostaining pattern. In our study, while c-ANCA were mainly found in patients with biopsy-proven Wegener's granulomatosis, MPO-ANCA identified those with idiopathic and polyarteritis nodosa-associated necrotizing and crescentic glomerulonephritis. In addition, pulmonary hemorrhage with necrotizing alveolar capillaritis as the main morphologic substrate occurred frequently among patients with MPO-ANCA, including three affected by polyarteritis nodosa and three who had pulmonary hemorrhage as the only clinical finding. On the other hand, these antibodies could be also detected in 30% of patients with a proven diagnosis of anti-glomerular basement membrane (GBM) disease. Irrespective of the primary underlying condition, the sensitivity and specificity of MPO-ANCA for pauci-immune necrotizing glomerulonephritis and alveolar capillaritis, either alone or in combination, were 75% and 98%, respectively, and their positive and negative predictive values were 81% and 97%, respectively. Therefore, the detection of these antibodies strongly supports this pathologic substrate in patients in whom histologic studies have not been performed or a definite diagnosis has not been established, thus facilitating therapeutic decisions in life-threatening conditions. Furthermore, since a small percentage of patients with anti-GBM disease are also found to have MPO-ANCA, it would be recommendable to systematically search for both MPO-ANCA and anti-GBM antibodies in any patient with a suspected diagnosis of rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. © 1992, National Kidney Foundation. All rights reserved. All rights reserved.