Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Classic anti-neutrophil cytoplasm antibodies (cANCA), perinuclear ANCA (pANCA) and antibodies directed against myeloperoxidase (MPO-Ab) were evaluated in 25 patients with either idiopathic or secondary rapidly progressive glomerulonephritis (RPGN). While cANCA were found almost exclusively in Wegener's granulomatosis, pANCA were detectable in several disorders, including microscopic polyarteritis (mPA), but also idiopathic RPGN. MPO-Ab were frequently found in sera from patients with all types of idiopathic but not of secondary RPGN. These results support the hypothesis that some cases of RPGN are early or limited forms of systematic vasculitis. We then looked for the presence of IgA-ANCA in Henoch-Schoenlein purpura (HSP): we found IgA-ANCA with immunoenzymatic assay but not with immunofluorescence in HSP, in primary IgA-GN and in membranous GN as well, thus suggesting the poor specificity of this type of ANCA. The possible pathologic implications of ANCA were examined in vitro. Serum samples from several patients with ANCA were assessed for their capacity to enhance chemiluminescence generation from resting or PMA-stimulated macrophages. Sera from RPGN and mPA patients displaying anti-MPO activity induced granulocytes to enhance the production of oxygen free radicals, thus suggesting a phlogistic effect of MPO-Ab positive sera.
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PMID:Classic and perinuclear anti-neutrophil cytoplasm antibodies and antimyeloperoxidase antibodies in rapidly progressive glomerulonephritis. 166 54

Antineutrophil cytoplasmatic autoantibodies (ANCA) have been tested in this laboratory for more than two years with a 3-fold increase in tests and positive results. The initial association with Wegener's granulomatosis has since been extended to microscopic polyarteritis and rapidly progressive glomerulonephritis. We review the published data. ANCA are not simply another laboratory test but have become an important tool for diagnosis, treatment monitoring and prevention of relapses in many vasculitis syndromes including some forms of rapidly progressive glomerulonephritis. The ANCA-associated antigens have been identified as a serin-proteinase and myeloperoxidase. This provides insights into the pathogenesis of the ANCA-related diseases.
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PMID:[Antineutrophil cytoplasma antibodies (ANCA): clinical indications and experience with these new autoantibodies]. 167 57

The antigenic specificity and clinical distribution of the antineutrophil cytoplasmic antibodies (ANCA) in kidney diseases have recently been extensively studied. In patients with systemic vasculitis, the great predominance of two major ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO), is now established. PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation, and thus are able to interact with autoantibodies after neutrophil preactivation. Furthermore, by comparison of amino acid and DNA sequences, it has been shown that PR3 is identical to myeloblastin, which has been described independently and is involved in the control of growth and differentiation of leukemic cells. Aside from the two major ANCA antigens, a number of neutrophil cytoplasmic antigens recognized by ANCA have been identified, including human leukocyte elastase, lactoferrin, CAP57, and cathepsin G. These rare ANCA specificities occur in a limited number of patients. The variety of ANCA antigen specificities contrasts, however, with the fact that the vast majority of ANCA-positive sera are monospecific for one single ANCA antigen. With regard to clinical distribution, ANCA have major diagnostic significance in the four conditions in which they are frequently detected: Wegener's granulomatosis (WG), Churg and Strauss Syndrome (CSS), microscopic periarteritis (MPA), and necrotic and crescentic glomerulonephritis (NCGN). However, the initial dichotomy between MPO-associated vasculitis (NCGN, MPA) and that associated with anti-PR3 antibodies (WG) appears far from absolute.
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PMID:Antigen specificities and clinical distribution of ANCA in kidney diseases. 172 65

Antineutrophil cytoplasmic autoantibodies (ANCA) specific for constituents of neutrophil primary granules and monocyte lysosomes have been demonstrated in various vasculitic disorders. The staining pattern in indirect immunofluorescence microscopy using alcohol-fixed neutrophils as substrate allows distinction among 3 types of ANCA: 1) classic anti-neutrophil cytoplasmic antibody (cANCA, formerly known as ACPA); 2) a type with a perinuclear/nuclear staining pattern produced when alcohol-fixed neutrophils are used as substrate (pANCA); and 3) a mixture of both of the above types (xANCA, also described recently as pANCA). Most cANCA are directed against proteinase 3 ("Wegener's autoantigen"). Some pANCA have specificity for myeloperoxidase and are associated with idiopathic crescentic glomerulonephritis ("renal vasculitis") and other systemic vasculitides exhibiting a paucity of immune deposits in blood vessels. In addition to being a useful serological marker, ANCA appear to be directly involved in the pathogenesis of systemic vasculitis. ANCA can activate cytokine-primed granulocytes and monocytes to undergo a respiratory burst and degranulation. This effect leads to vasculitis through the attachment of these cells to the vascular endothelium primed by cytokine-induced expression of adhesion molecules (E-LAM 1) on the endothelium. Thus, the release of toxic oxygen radicals and lytic enzymes is capable of causing vascular damage. In the present paper we report on the main target antigens and on the history, nomenclature, laboratory methods, and etiopathological implication of ANCA. Additional pathophysiological aspects of ANCA and/or autoreactive T cells and immunoregulatory events are also discussed.
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PMID:Antineutrophil cytoplasmic autoantibodies: immunobiological aspects. 172 66

Granulomatous meningitis was present in 6/33 bovine fetuses from which Brucella abortus (B. abortus) had been isolated. Meningitis was severe in three fetuses, moderate in one fetus, and mild in the remaining two fetuses. The meningitis was characterized by the infiltration of a mixed population of lymphocytes, plasma cells, and macrophages in the leptomeninges. Vasculitis characterized by the infiltration of lymphocytes and plasma cells in the vascular wall was observed in the vessels of the cerebral cortices of 4/6 fetuses. Gram negative coccobacilli were present in the cytoplasm of the leptomeningeal macrophages and extracellularly. Brucellar antigens labeled by the avidin-biotin-peroxidase complex method were present in massive amounts in leptomeningeal macrophages and in small foci of stained cells in the choroid plexus and ependyma. The findings indicate that B. abortus is one of pathogens capable of inducing meningitis in bovine fetuses.
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PMID:Brucella abortus-associated meningitis in aborted bovine fetuses. 177 39

We have compared the role of tumor necrosis factor (TNF) in the pathogenesis of analogous acute immune complex-induced lung and dermal vascular injury models in rats. Intratracheal administration of IgG anti-bovine serum albumin (BSA), followed immediately by intravenous infusion of BSA, results in acute neutrophil-mediated alveolitis. Neutralization of intrapulmonary TNF activity with anti-TNF antibodies resulted in reduced pulmonary neutrophil recruitment and marked attenuation of lung injury. Intradermal injection of IgG anti-BSA, followed by intravenous BSA, results in acute neutrophil-mediated dermal vasculitis. Neither locally nor systemically administered anti-TNF antibodies reduced dermal vascular injury as measured by local hemorrhage and vasopermeability changes. Based on morphometric analysis and measurements of myeloperoxidase in tissue extracts, anti-TNF antibodies had no effect on dermal neutrophil recruitment. Intradermal and intrapulmonary administration of physiologic concentrations of recombinant human TNF resulted in modest, dose-dependent increases in local vasopermeability accompanied by negligible neutrophil recruitment. Administration of higher concentrations of TNF resulted in increases in both local vasopermeability and neutrophil recruitment. These data suggest that while both rat pulmonary and dermal blood vessels can respond to TNF-triggered proinflammatory events, endogenous TNF plays a much greater role in acute alveolitis than in dermal vasculitis.
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PMID:Disparate roles for TNF in the pathogenesis of acute immune complex alveolitis and dermal vasculitis. 183 7

In view of the supposed hypersensitivity, the elevated levels of IgE, and the occurrence of eosinophilia reported in Wegener's granulomatosis and related conditions, we studied the IgG subclass distribution of ANCA directed against a 29-kD serine protease and myeloperoxidase (MPO) in 41 untreated ANCA-positive patients with several forms of active vasculitis and/or glomerulonephritis. We found that both 29-kD ANCA and MPO ANCA were predominantly of the IgG1 and IgG4 subclass in all groups of patients. The additional presence of IgG3 subclass was associated with renal involvement. We compared the subclass distribution of ANCA with that of total IgG subclass levels, and with the IgG subclass distribution of antibodies to cytomegalovirus (CMV) as a persistent endogenous antigen and antibodies to tetanus toxoid (TT) as an exogenous recall antigen. Total levels of IgG4 were elevated in the majority of the patients together with elevated IgG1 levels. Antibodies to CMV and TT, however, had the same subclass distribution as found in normals and did not show enhanced IgG4 expression. ANCA belong predominantly to the IgG1 and IgG4 subclass, which may suggest that the production of ANCA is related to recurrent exposition to the antigen(s) involved, possibly as part of a hypersensitivity reaction.
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PMID:Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders. 184 89

Antineutrophil cytoplasmic autoantibodies (ANCA) are present in patients with systemic vasculitis with or without renal involvement. These antibodies were first seen using indirect immunofluorescence (IIF). Two types of patterns are seen on ethanol-fixed neutrophils: the cytoplasmic and the perinuclear pattern. The cytoplasmic pattern is called C-ANCA (classical or cytoplasmic ANCA) and the perinuclear, P-ANCA. Antibodies to a serine proteinase, called proteinase 3 or myeloblastin, give rise to the C-ANCA pattern, while antibodies to myeloperoxidase give rise to the P-ANCA pattern. Proteinase 3, as well as myeloperoxidase, is present in the primary granules of neutrophils, and the P-ANCA pattern is thus an artifactual staining pattern. Myeloperoxidase, which is a basic protein, redistributes during ethanol fixation from the primary granules to the negatively charged nucleus. As an alternative to the IF technique, several solid-phase assays have been developed using either 125I or enzyme-labeled secondary antibodies. Depending on the degree of purification of the antigens used, such assays may be used for screening or as a complement to the IF method. Today it is possible to directly screen for both types of ANCA using enzyme-linked immunosorbent assay (ELISA). Simultaneous screening for antiglomerular basement membrane (GBM) antibodies (Goodpasture antibodies) increases the diagnostic yield, especially in patients with renopulmonary syndromes.
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PMID:How are antineutrophil cytoplasmic autoantibodies detected? 186 72

Five patients with subglottic stenosis, occurring either as a presenting symptom or as a manifestation in the course of a systemic disease, are described. Indirect immunofluorescence revealed the presence of circulating autoantibodies against both cytoplasmic and perinuclear constituents of neutrophils in all five. Antibodies directed against a 29 kDa antigen of the azurophilic granules (two patients), against myeloperoxidase (one patient), and against both the 29 kDa antigen and myeloperoxidase (one patient) were found by enzyme-linked immunosorbent assay. These autoantibodies have previously been found in patients with Wegener's granulomatosis, microscopic polyarteritis, (idiopathic) glomerulonephritis and Churg-Strauss syndrome. However, only one of these five patients fulfilled the criteria for these conditions. Since these autoantibodies are seldom observed in other conditions, and other diseases had been excluded by careful evaluation, we suggest that their presence places subglottic stenosis within the spectrum of necrotizing (granulomatous) vasculitis. Whether immunosuppressive therapy is always warranted in patients with subglottic stenosis and circulating anti-neutrophil cytoplasmic antibodies is a matter of debate.
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PMID:Circulating anti-neutrophil cytoplasmic autoantibodies in subglottic stenosis: a useful aid in diagnosing vasculitis in this condition? 194 37

Anti-neutrophil cytoplasmic antibodies (ANCA) have been found in patients with systemic vasculitis and crescentic glomerulonephritis. Recently two types of ANCA were identified, one is anti-myeloperoxidase antibodies (Anti-MPO Ab) stained perinuclear pattern of alcohol-fixed neutrophils by immunofluorescence test, and the other is autoantibodies with no reactivity with myeloperoxidase stained diffuse cytoplasmic pattern (C-ANCA). We investigated 59 patients with various glomerulonephritis with or without crescent to detect anti-MPO Ab and C-ANCA by an enzyme-linked immunosorbent assay. The results were as follows: 1) Anti-MPO Ab were detected only in patients with various glomerulonephritis with crescent. 2) Titers of anti-MPO Ab were high related to percentage of crescent in some cases of glomerulonephritis. 3) Titers of anti-MPO Ab were elevated at stage of cellular and fibro-cellular crescent. 4) C-ANCA were detected only in patients with Wegener's granulomatosis. These data suggested that anti-MPO Ab may play important roles in crescent formation and may be a marker of crescent formation in various glomerulonephritis.
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PMID:[Clinical investigation of anti-myeloperoxidase antibodies in patients with glomerulonephritis with crescent formation]. 196 27


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