ANTIPROTEINASE-3 ANTIBODIES, THEIR CHARACTERIZATION AND DISEASE ASSOCIATIONS

Anti-proteinase 3 antibodies are a subgroup of anti-neutrophil cytopla smic antibodies (ANCA), and we have established an ELISA for their det ection using high performance liquid chromatograhy (HPLC)-purified pro tein. This assay is sensitive and specific: inhibition studies have sh own that despite the homology between proteinase 3 and elastase there is no cross-reactivity between the corresponding antibodies for their targets. Anti-proteinase 3 antibodies were associated most often with cytoplasmic fluorescence (17/22, 77%), but occasionally with a perinuc lear (3/22, 14%) or atypical pattern (1/2). These antibodies were foun d in 23 out of 76 sera (30%) that were positive in an ELISA based on a crude neutrophil cytoplasmic extract, and they were associated with b oth 29 and 55 kD bands on Western blots. Anti-proteinase 3 antibodies were found in most individuals with active Wegener's granulomatosis (1 0/13, 77%), but less often in individuals with microscopic polyarterit is (2/10, 20%) or segmental necrotizing glomerulonephritis (3/6, 50%). However, antiproteinase 3 antibodies were not detected in any of 32 s era from individuals with rheumatoid arthritis or systemic lupus eryth ematosus (SLE). Occasionally anti-proteinase 3 antibodies were associa ted with anti-glomerular basement membrane antibodies (1/11, 9%) or wi th anti-myeloperoxidase antibodies(1/11, 9%). IgM anti-proteinase 3 an tibodies were uncommon (2/22 sera, 9%), and no IgA antibodies were dem onstrated in any of 22 sera from patients with active systemic vasculi tis. Significantly more individuals presented with anti-proteinase 3 a ntibodies in April-May-June, suggesting that an infective agent preval ent in Autumn might have a causative role in the associated diseases. Anti-proteinase 3 antibodies are the most common target antigen associ ated with Wegener's granulomatosis and cytoplasmic fluorescence.