SUMMARY Anti‐neutrophil cytoplasm antibodies (ANCA) are markers of systemic vasculitis for which a pathogenetic role has been postulated. We have examined the effect of these autoantibodies on the function of normal human neutrophils in vitro. In the presence of ANCA positive sera luminolamplified chemiluminescence was significantly increased compared to the values seen in the presence of normal or anti‐double stranded DNA positive sera (P<0.01). Five of six ANCA positive F(ab)2 preparations also produced significant neutrophil activation as demonstrated by the chemiluminescence response. This response was totally abrogated by the addition of neutrophil cytoplasm extract, containing the ANCA antigen. Addition of inhibitors to the chemiluminesccnce system demonstrated that the chemiluminescence response was inhibited by azide and salicylhydroxamic acid and reduced by histidine, suggesting that the chemiluminescence response was due to activation of myeloperoxidase, with generation of singlet oxygen. The chemotactic response to f‐Met‐Leu‐Phe, a bacterial chemotactic peptide, was significantly augmented in the presence of ANCA. Chemotaxis to zymosan‐activated serum and chemokinesis was not affected. Phagocytosis was also unaffected. We propose that neutrophil activation and modulation of neutrophil migration by ANCA may be of pathogenetic significance in systemic vasculitis.

Crescentic glomerulonephritis is usually classified into antiglomerular basement membrane (GBM) disease, immune-complex disease, or pauci-immune crescentic nephritis. The last category includes patients with systemic vasculitis as well as 'idiopathic' isolated crescentic nephritis. The presence of anti-neutrophil cytoplasmic antibodies (ANCA) in many patients with apparently isolated crescentic nephritis suggests that this represents a renal-limited form of vasculitis, and that truly 'idiopathic' crescentic nephritis is a very rare entity. We reviewed all renal biopsies with extracapillary proliferation seen at our centre since the availability of an ANCA assay (4-year period). There were 89 such biopsies of a total of 1240, of which 82 had sufficient details for further analysis. Of these, 10 had anti-GBM disease, 35 had epithelial proliferation associated with a variety of other diseases, and 36 had ANCA-associated disease. Nine of this last group had no extrarenal features and would previously have been classified as 'idiopathic' crescentic glomerulonephritis. The single remaining patient had an inactive glomerulonephritis with a scarred crescent; the predominant lesion was an interstitial nephritis. We therefore conclude that truly 'idiopathic' crescentic nephritis is very rare, if it exists at all. The ability to provide a practically complete classification of crescentic nephritis has important prognostic and therapeutic consequences.

SUMMARYANCA are associated with certain forms of systemic vasculitis, and have been reported previously to be of Ihe IgG and IgM isotype. We examined ihc possible association between IgA ANCA and the IgA-relaled diseases Henoch-Schonlein purpura (HSP) and IgA nephropaihy (IgAN). IgA and IgG ANCA were detected by isotype-specifie solid-phase assays with a erude neutrophil extract, and their presence was confirmed by antigen-specific fluid-phase competitive inhibition tests and by indirect inimunofiuorescence. The possible interference by IgA rheumatoid faeior was excluded. IgA ANCA were detected in sera from 11/I4 HSP patients (79%). from 1/30 IgAN paLicnts 0"A>), from 1/40 patients with vasculitldes classically associated with IgG ANCA (2-5%), and in none or60 sera from healthy blood donors. IgG ANCA were present with IgA ANCA in three patients with HSP. Only one HSP serum had anti-myeloperoxidase (MPO) activity by both IgA and IgG isotypc-specific ELISA, and none was positive for proteinase 3 (PR3). Western blot analysis performed with neutrophil extract showed that the four strongest IgA ANCA-positive HSP sera reacted with a 51-kD protein; Western blot performed on cellular fractions showed that this protein is primarily membrane-assoeiated, and different from fibronectin. Our study suggests that adult HSP is elosely associated with cireulating IgA ANCA. which may be directed against a different autoantigen than that recognized by IgG ANCA.