SOME PATIENTS WITH ANTIMYELOPEROXIDASE AUTOANTIBODIES HAVE A C-ANCA PATTERN

Rapidly progressive glomerulonephritis with or without other signs of systemic vasculitis is often accompanied by antibodies to myeloperoxid ase. Such antibodies normally produce a perinuclear pattern on ethanol -fixed neutrophils (perinuclear anti-neutrophil cytoplasm antibodies ( P-ANCA)) at indirect immunofluorescence. We report here sera from thre e patients that are antimyeloperoxidase-positive in ELISA. that instea d produce a cytoplasmic pattern (classical antineutrophil cytoplasmic antibodies (C-ANCA)), a pattern normally seen in conjunction with anti bodies to proteinase 3. These sera did not react with proteinase 3. Fo r two of the sera the specificity of the anti-myeloperoxidase reaction was confirmed with inhibition-ELISA experiments and with immunoblotti ng. A mouse anti-myeloperoxidase MoAb that produces a cytoplasmic patt ern is also described. Competition ELISA experiments show that this an tibody and antimyeloperoxidase sera with cytoplasmic pattern recognize epitopes that are separate from epitopes recognized by another perinu clear pattern producing anti-myeloperoxidase MoAb. 'Cytoplasmic patter n' epitopes as well as 'perinuclear pattern' epitopes can be found on all three major myeloperoxidase isoforms, after separation by ion exch ange chromatography. Affinity chromatography, using the cytoplasmic pa ttern producing anti-myeloperoxidase monoclonal antibody, shows that t he epitope recognized by this MoAb is present on all myeloperoxidase m olecules. This epitope is not confined to any special subpopulation. T hese findings indicate that all myeloperoxidase do not relocate after ethanol fixation, and that C-ANCA and P-ANCA epitopes exist simultaneo usly on the same myeloperoxidase molecule. We propose that the two imm unofluorescence patterns arise due to different availabilities of the epitopes in the microenvironment where myeloperoxidase is present.