Association of autoantibodies to myeloperoxidase with different forms of vasculitis

Abstract

Antineutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase (MPO) were found in 53 patient sera that were routinely submitted for antineutrophil cytoplasmic antibody determination. Based on clinical and histologic criteria, 15 of these 53 patients were classified as having systemic necrotizing vasculitis of the polyarteritis group, 11 patients were classified as having Wegener's granulomatosis (WG), and 14 were classified as having idiopathic crescentic glomerulonephritis. The remaining 13 patients did not fulfill the diagnostic criteria for these disorders, although most of these patients had clinical symptoms compatible with these disorders. While all patients with WG had renal involvement, only 4 of the 15 patients with systemic necrotizing vasculitis of the polyarteritis group had glomerulonephritis. The sensitivity of autoantibodies to MPO for either systemic necrotizing vasculitis of the polyarteritis group, WG, or idiopathic crescentic glomerulonephritis was further tested in all our patients with these disorders (n = 104). Twenty-seven of 104 patients had autoantibodies to MPO. Furthermore, 69 of the remaining 77 patients had autoantibodies specific for the 29-kd serine protease, which has been reported to be specifically associated with WG. Sera from 8 patients were negative for either of these antibodies (92% sensitivity of autoantibodies to MPO and/or the 29-kd mine protease). The specificity of autoantibodies to MPO for either systemic necrotizing vasculitis of the polyarteritis group, WG, or idiopathic crescentic glomerulonephritis was also tested in selected groups of patients who had closely related diseases. Two of 144 patients had autoantibodies to MPO (specificity 99%). We conclude that these antibodies are not only associated with idiopathic and vasculitis-associated crescentic glomerulonephritis, but also with classic polyarteritis nodosa, Churg-Strauss syndrome, and the polyangiitis overlap syndrome without renal involvement. The presence of autoantibodies to MPO or the 29-kd serine protease is highly sensitive and specific for systemic necrotizing vasculitis of the polyarteritis group, WG, and idiopathic crescentic glomerulonephritis.The connective tissue diseases are associated with autoantibodies to various non-organ-specific antigens, particularly nuclear antigens (1). The sensitivity and specificity of these autoantibodies for certain disease entities or disease subsets are generally well delineated. In systemic necrotizing vasculitis, however, laboratory tests are generally considered nondiagnostic (2,3).During the last few years, anticytoplasmic autoantibodies or antineutrophil cytoplasmic autoantibod-

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

“…Thereafter, it was recognized that ANCA was observed in GPA [53] and that the target antigen of ANCA in these patients was proteinase 3. Furthermore, MPO was found to be the target antigen in patients with PR3-ANCA-negative GPA, MPA and/or EGPA [14,54,55]. Importantly, patients with necrotizing glomerulonephritis are nearly always ANCA positive [14,55] while ANCA are not always found in a subgroup of patients with more limited disease [56,57].…”

“…Furthermore, MPO was found to be the target antigen in patients with PR3-ANCA-negative GPA, MPA and/or EGPA [14,54,55]. Importantly, patients with necrotizing glomerulonephritis are nearly always ANCA positive [14,55] while ANCA are not always found in a subgroup of patients with more limited disease [56,57]. The presence of PR3-or MPO-ANCA in AAV has been undisputed and has been incorporated in the current classification schemes [12,15].…”

Epigenetics and Vasculitis: a Comprehensive Review

“…Although ANCA can be induced by certain infections, they are an AAV hallmark for which there are circulating ANCA that primarily target myeloperoxidase (MPO-ANCA) or serine protease proteinase 3 (PR3-ANCA) [38]. It should be noted that AAV can be accompanied by both MPO-ANCA and PR3-ANCA [33,39].…”

Serum markers of T cell activation in relapses of Wegener's granulomatosis

“…Antineutrophil cytoplasmic antibodies (ANCA) directed against lysosomal enzymes of neutrophils and monocytes. in particular Proteinase 3 and myeloperoxidase, have been (ound to be strongly associated with this disease and other forms of idiopathic necrotizing vasculitis and crcscentic glomeruloiiephritis [2][3][4][5][6]. Changes In levels of these antibodies correlate closely with disease activity, which may suggest a pathophysiologieal role for these autoantibodies [2,7,8J. Apart from humoral mechanisms, cell-mediated immunity may also be involved in thepalhogenesisofWG [9], A role for T cell involvement in WG is suggested by the presence of granulomas, which points to T cell-mediated delayed type hypersensitivity reactions lo an as yet unknown stimulus.…”