Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis.
Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with clinically proven vasculitis have been described as reacting with proteins present in the granules of human neutrophils. We have studied sera from 59 ANCA positive patients to further characterize the antibody response. In addition to the antigens previously identified in the vasculitic syndromes (myeloperoxidase and serine proteinase 3) the majority of these sera contained antibodies that reacted with a cytosolic extract of neutrophils on Western blots. Nearly 40% of these sera had antibodies directed against a cytosolic protein(s) of molecular mass 48 kD. This protein was purified from neutrophil cytosol by ammonium sulphate fractionation, anion exchange and reverse phase chromatography. Amino acid sequence analysis of a proteolytic fragment of this protein identified it as alpha enolase. The anti-enolase antibodies only recognized the alpha isoform and were present in sera giving either a pANCA or cANCA staining pattern by indirect immunofluorescence. Antibodies to alpha enolase were also found in sera from patients with systemic lupus erythematosus, particularly those with renal disease. We conclude that the antibody response in ANCA positive vasculitis is not restricted to neutrophil granule proteins.
Moodie
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FD
Department of Medicine, Institute of Nephrology and Urology, University College London, England, United Kingdom.
Leaker
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B
Cambridge
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Totty
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Segal
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AW
D000595:Amino Acid Sequence; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D003600:Cytosol / Q000201:enzymology / Q000276:immunology; D006801:Humans; D008181:Lupus Nephritis / Q000201:enzymology / Q000276:immunology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000097:blood / Q000276:immunology*; D014657:Vasculitis / Q000201:enzymology / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D001324:Autoantigens; D010751:Phosphopyruvate Hydratase