Autoantibodies staining the nuclei or the perinuclear zone of neutrophils by indirect immunofluorescence are referred to as pANCA whereas those giving a clear cytoplasmic fluorescence are referred to as cANCA. The antigen recognised by most pANCA sera has been identified as myeloperoxidase.
Autoantibodies to MPO are found in the sera of patients with various types of systemic vasculitis including idiopathic crescentic glomerulonephritis, Churg-Strauss syndrome, microscopic polyangiitis and polarteritis nodosa. Anti-myeloperoxidase antibodies have also been reported in some patients with Wegener's granulomatosis, and occasionally in patients with rheumatoid arthritis or inflammatory bowel disease.
The heme-containing glycoprotein myeloperoxidase is a major constituent of neutrophil azurophilic granules and plays a major role in the oxygen-dependent microbicidal system of these cells. This enzyme catalyses the oxidation of chloride by hydrogen peroxide to produce the highly reactive reagent hypochlorous acid.
When isolated from mature neutrophil granulocytes, myeloperoxidase consists of a tetramer composed of two 59 kDa and two 12 kDa subunits that are evident under reducing SDS-electrophoresis. Myeloperoxidase cDNA has been cloned and sequenced, revealing that the protein is synthesised as an 80 kDa precursor before it is processed into the 59 and 12 kDa subunits of 467 and 113 amino acids respectively.
Autoantibodies to MPO appear to recognise conformational epitopes. The use of purified myeloperoxidase for the detection of anti-myeloperoxidase autoantibodies by solid-phase ELISA has been described by several authors.
Idiopathic Crescentic Glomerulonephritis
Elevated plasma levels in acute coronary syndromes and some malignant
Davies, D.J. et al. (1982) Br. Med. J. 285, 606
Wiik, A. et al. (1994) Man. Biol. Markers of Dis. (Kluwer Acad.Publ.) A9:1-14
Falk, R.J. & Jennette, J.C. (1988) N. Engl. J. Med. 316, 1651
Falk, R.J. et al. (1990) Neth. J. Med. 36, 121-125
Lee, S.S. et al. (1990) Clin. Exp. Immunol. 79, 41-46
Cohen Tervaert, R. et al. (1990) Arthr. Rheum. 33, 1264
Gueirard, P. et al. (1991) J. Autoimmun. 4, 517
Ulmer, M. (1992) Clin. Nephrol. 37, 161
Kallenberg, C.G.M. et al. (1994) Kidney Int. 46, 1
Cambridge, G. et al. (1994) Ann. Rheum. Dis. 53, 241
Snook, J.A. (1989) Clin. Exp. Immunol. 76, 301
Klebanoff, S.J. (1968) J. Bacteriol. 95, 21311
Harrison, J.E. & Schultz, J. (1976) J. Biol. Chem. 251, 13711
Olsen, R.L. & Little, C. (1984) Biochem. J. 222, 7011
Falk, R.J. et al. (1992) Clin. Exp. Immunol. 89, 274