ANTI-NATIVE AND RECOMBINANT MYELOPEROXIDASE MONOCLONALS AND HUMAN AUTOANTIBODIES

Myeloperoxidase (MPO) is one of the main antigen targets of anti-neutr ophil cytoplasmic antibodies (ANCA) in systemic vasculitides. It has b een suggested that anti-MPO antibodies may recognize a single epitope on recombinant MPO. If confirmed on native MPO, this might allow speci fic therapeutic intervention with anti-idiotypic MoAbs to prevent anti body-antigen interaction which is thought to cause activation of neutr ophils and vasculitis. We searched for restriction in the epitope reco gnition profile in 50 patients with anti-MPO autoantibodies, using bot h native and recombinant MPO. Mouse monoclonals were purified and test ed in competition assays. At least four epitopes were identified on na tive MPO using these monoclonals and only two were conserved on recomb inant MPO. We found that human MPO autoantibody response was not restr icted to a single epitope on native MPO, as all sera tested did not sh ow the same profile in competitive studies with monoclonals. Furthermo re, 30% of human anti-native MPO sera failed to recognize rMPO.