title: Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase.
abstract: We wondered whether anti-myeloperoxidase (MPO) autoantibodies (MPO-ANCA) found in patients with systemic vasculitis react with a conformational epitope or epitopes on the MPO molecule. Sera from 15 human MPO-ANCA, and a polyclonal and a monoclonal anti-MPO antibodies were reacted with MPO in native and denatured states. Human MPO-ANCA and mouse monoclonal anti-MPO reacted with native MPO, and a 120-kD band representing the MPO hologenzyme, but not with denatured MPO fragments; however, MPO-ANCA and mouse anti-MPO did not demonstrate competitive inhibition of binding to MPO. Polyclonal rabbit anti-MPO reacted with both native and denatured MPO. All MPO-ANCA tested showed the same patterns of reactivity with native and denatured MPO in dot blot and Western blot analyses. Both polyclonal and monoclonal anti-MPO antibodies inhibited MPO's protein iodination by over 90%, whereas MPO-ANCA IgGs, normal IgGs and disease control IgGs did not. These data suggest that (i) MPO-ANCA interact with a conformational epitope on the MPO molecule; and (ii) MPO-ANCA from different patients have similar reactivity with native versus denatured MPO.
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill.
authors.forename: R J
authors.initials: RJ
authors.lastname: Falk
authors.forename: M
authors.initials: M
authors.lastname: Becker
authors.forename: R
authors.initials: R
authors.lastname: Terrell
authors.forename: J C
authors.initials: JC
authors.lastname: Jennette
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D000939:Epitopes; D006801:Humans; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000276:immunology*; D011489:Protein Denaturation
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D000939:Epitopes; D009195:Peroxidase