Correlation of antineutrophil cytoplasmic antibodies with the extrarenal histopathology of Wegener's (pathergic) granulomatosis and related forms of vasculitis.

We studied the histologic findings from extrarenal biopsies (especially of the lung or upper respiratory tract) or autopsies of 68 patients who were tested for serum antineutrophil cytoplasmic antibodies (ANCAs). We used antigen-specific assays to detect antibodies against proteinase 3 (PR3) and myeloperoxidase (MPO), the two types of ANCAs of proven diagnostic value for the spectrum of diseases that includes Wegener's (pathergic) granulomatosis, microscopic polyarteritis (microscopic polyangiitis), Churg-Strauss syndrome, idiopathic necrotizing and crescentic glomerulonephritis, and their variants. Twenty-eight patients had antibodies to PR3 and 16 had antibodies to MPO; no patient had antibodies to both.

Value of tests for antineutrophil cytoplasmic autoantibodies in the diagnosis and treatment of vasculitis.

The diagnosis and classification of vasculitis has been revolutionized by the discovery and characterization of serum antineutrophil cytoplasmic autoantibodies. These autoantibodies are highly specific, objective markers for the major subset of vasculitis that includes Wegener's granulomatosis, polyarteritis nodosa (microscopic polyangiitis), Churg-Strauss syndrome, primary or idiopathic pauciimmune necrotizing and crescentic glomerulonephritis with or without pulmonary hemorrhage, as well as some poorly characterized and overlapping forms of these vasculitides. The finding of antineutrophil cytoplasmic antibodies throughout this group identifies these syndromes as a single category or spectrum of disease.

Antineutrophil cytoplasmic autoantibody-associated vasculitis presenting as Sjögren's syndrome.

A 63-year-old woman, in whom a diagnosis of Sjögren's syndrome was initially made, proved to have systemic vasculitis with salivary gland involvement and necrotizing and crescentic glomerulonephritis. Antineutrophil cytoplasmic autoantibodies (ANCA) against myeloperoxidase were positive. ANCA-associated vasculitis should be considered in the differential diagnosis of Sjögren's syndrome.

Clinical utility of fine needle aspiration biopsy in the diagnosis of Wegener's granulomatosis. A report of two cases.

In two patients, pulmonary lesions of Wegener's granulomatosis (WG) were sampled by fine needle aspiration biopsy: one with the clinical diagnosis of primary pulmonary malignancy and the other with a clinical suspicion of WG. In the latter case the smears showed distinctive eosinophilic, collagen necrosis (pathergic necrosis), poorly formed granulomata composed of loose aggregates of elongated, often palisading epithelioid histiocytes, and multinucleate histiocytes. A cell block preparation in this case contained minute tissue fragments illustrating the distinctive, pathergic-type necrosis.

Diagnostic value of anti-neutrophil cytoplasmic antibodies in scleritis associated with Wegener's granulomatosis.

Serum antineutrophil cytoplasmic antibodies (ANCAs) are a sensitive and specific marker for generalized Wegener's granulomatosis. However, ANCA sensitivity and specificity in identifying patients in whom ophthalmic signs constitute the presenting or only definitive manifestation of Wegener's granulomatosis have not been tested. The authors report on 7 patients in whom scleritis was the initial manifestation leading to the diagnosis of Wegener's granulomatosis.

Antigen-specific radioimmunoassays for anti-neutrophil cytoplasmic antibodies in the diagnosis of rapidly progressive glomerulonephritis.

Circulating anti-neutrophil cytoplasmic antibodies (ANCA) have been described in most patients with "pauci-immune" necrotizing and crescentic glomerulonephritis. A 29-kDa serine protease (p29 or proteinase 3) and myeloperoxidase are the two best characterized antigens recognized by ANCA. The study presented here was conducted to define the diagnostic value of assays for antibodies against these two antigens in rapidly progressive glomerulonephritis.

Loss of antigens associated with the apical endocytotic pathway in proximal tubules from rats with heymann nephritis.

In addition to the glomerular lesions associated with Heymann nephritis, a rat model of human membranous nephritis, proximal tubule damage, and a perturbation of proximal tubule function also have been reported to occur in this disease. The aim of the present study was to examine in more detail the nature of the apical plasma membrane damage in proximal tubules using specific antibodies directed against clathrin, gp330, and a proton-pumping adenosine triphosphatase, all of which are components of the apical endocytotic apparatus of these epithelial cells. Immunocytochemical studies revealed a marked reduction in staining for all three antigens in proximal tubules from rats with active Heymann nephritis.

Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase.

Circulating IgG autoantibodies that produce cytoplasmic immunofluorescence staining of ethanol-fixed normal neutrophils have recently been found in a large percentage of patients with active Wegener's granulomatosis. Such autoantibodies are rarely found in other diseases and are therefore virtually diagnostic of Wegener's granulomatosis. The nature of the neutrophil antigen defined by these autoantibodies is controversial and the roles of the antigen and/or autoantibodies in the pathogenesis of Wegener's granulomatosis are unknown.

Colchicine-induced redistribution of an apical membrane glycoprotein (gp330) in proximal tubules.

Factors governing the selective, polarized insertion of membrane proteins are poorly understood, but some studies have suggested that microtubules are involved in the generation and maintenance of cell polarity. We have examined by immunocytochemistry the effect of the microtubule-disrupting agent, colchicine, on the cellular distribution of an endogenous glycoprotein, gp330, which is normally inserted only into the apical plasma membrane of proximal tubule epithelial cells. In control rats, gp330 was localized in the brush border and in apical invaginations and vesicles.

Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor.

The pathogenesis of Heymann nephritis, a rat model of human membranous glomerulonephritis, depends on the interaction of autoantibodies with a renal glycoprotein (GP330) on glomerular podocytes. Partial complementary DNAs coding for GP330 were isolated and sequenced. The deduced amino acid sequence from 4.