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)

Extracapillary crescent is an elementary lesion which can be superimposed to any type of glomerulonephritis, or constitute the main lesion as in vasculitis, or appear to be idiopathic. One must oppose cellular crescent which is partially reversible, to irreversible fibrous crescent. Cellular composition of crescents has been much controversial: initially considered as having an epithelial-cell origin, then an exclusive macrophagic origin, crescents are in fact composed of epithelial cells, monocytes-macrophages and lymphocytes all together. The former are prevailing when Bowman's capsule (BC) is intact, whereas macrophages predominate when there is extensive damage of GBM and of BC. The initial event in crescent formation appear to be breaches in glomerular capillary wall, leading the deposition of fibrin within Bowman's space. The consequence is the proliferation of parietal epithelial cells and of activated macrophages followed by a production, in series, of cytokines and growth factors.
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PMID:[Crescent: structure, evolution, pathogenesis]. 129 81

The diagnostic potential of assays detecting anti-neutrophil cytoplasm antibodies (ANCA), anti-GBM antibodies and anti-dsDNA antibodies was evaluated by examining sera from time of admission in a consecutive series of 455 patients with biopsy verified primary or secondary glomerulonephritis (GN). ANCA were classified into c- and p-ANCA by indirect immunofluorescence (IIF) and ELISAs using alfa-granule extract, proteinase-3, myeloperoxidase (MPO), elastase and lactoferrin. C-ANCA was virtually confined to 64 patients with systemic small vessel vasculitis, 66-74% being c-ANCA positive. P-ANCA against MPO, seen in 47 patients, segregated through many diagnostic categories of primary and secondary severe GN. ANCA against lactoferrin and elastase were rare. Anti-dsDNA positive patients constituted 57% of the 44 ANA-positive patients with systemic lupus erythematosus. It is concluded that the IIF and ELISAs for anti-proteinase-3, anti-MPO, anti-dsDNA and anti-GBM have an acceptable performance and are useful in the primary diagnostic work-up of patients suspected for secondary GN as the majority of such patients will be classified by these assays.
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PMID:Anti-neutrophil cytoplasm antibodies, anti-GBM antibodies and anti-dsDNA antibodies in glomerulonephritis. 147 49

Anti-neutrophil cytoplasmic autoantibodies (ANCA) were detected in 12 out of 37 (32%) serum samples from patients with anti-glomerular basement membrane (GMB) disease by an indirect immunofluorescence assay. In 11 cases, ANCA were directed against myeloperoxidase, as revealed employing neutrophils devoid of this enzyme as the test substrate. Patients having both ANCA and anti-GBM antibodies (AGBMA) were considerably older (mean age 59 years) than patients with AGBMA alone (mean age 33 years). In addition, patients with both antibodies had some clinical and pathologic data that suggested an associated systemic vasculitis. This was supported by the fact that among these patients, those with highest ANCA titres recovered renal function despite being initially on hemodialysis, as opposed to those with lowest ANCA titres or AGBMA alone. In patients with both antibodies, there was an inverse relationship between AGBMA and ANCA values (p = 0.02). Moreover, the mean AGBMA level tended to be higher for patients with AGBMA alone than for those with both ANCA and AGBMA. These results suggest that, at least in some cases, there may be a contribution of an ANCA-related mechanism in the pathogenesis of anti-GBM disease. Although the exact role of ANCA in this and other diseases remains to be clarified, there is important clinical evidence that in anti-GBM disease ANCA may represent a serologic marker of good prognosis identifying a subset of patients who may recover renal function.
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PMID:Prognostic implication of anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in anti-glomerular basement membrane disease. 165 70

We have studied 495 sera that were referred to us from patients suspected on clinical and/or histological grounds to have a small vessel vasculitis. These sera were tested for antibodies against neutrophil cytoplasm antigens (anti-neutrophil cytoplasm antibodies, ANCA) using assays based on neutrophil acid extract, myeloperoxidase and elastase. Such antibodies are commonly found in Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA), and sometimes in other small vessel vasculitides. One hundred and twenty-six of these sera (25%) were positive in the acid extract ELISA, 68 (14%) in the assay for anti-myeloperoxidase antibodies and 35 (16%) in the assay for anti-elastase antibodies. A total of 166 sera (34%) were positive for antibodies against neutrophil cytoplasm constituents. No ANCA, anti-myeloperoxidase or anti-elastase antibodies were detected in 26 convalescent sera from patients either with WG or MPA, or who had previously been positive. The mean time between positive and negative sera was eight weeks (range three weeks to six months) and three out of three who relapsed again developed ANCA of the same specificity as the original sera. Of the 228 sera also tested for anti-GBM antibodies, 13 (5.7%) were positive. All these contained antibodies against neutrophil cytoplasm constituents (three against the acid extract, eight against myeloperoxidase and two against elastase). Forty-nine of the 74 sera (66%) tested for ANA were positive. Twenty-nine (39%) had a speckled and 20 (27%) had a homogeneous pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoantibodies in systemic vasculitis. 132 37

We report a case of idiopathic crescentic glomerulonephritis with pulmonary hemorrhage associated with anti-myeloperoxidase antibodies (anti-MPO ab). A 74 year-old female was admitted to our hospital because of rapidly progressive glomerulonephritic syndrome and dyspnea with bloody sputum. On admission anti-MPO ab, one of anti-neutrophil cytoplasmic antibodies, were detected but anti-GBM antibodies and immune complexes were not detected. Renal biopsy showed crescentic glomerulonephritis and lung biopsy showed massive alveolar hemorrhage. Both tissue had pauci-immune deposit by immunofluorescence microscopy. Hemodialysis and steroid administration were started. Pulmonary hemorrhage was improved remarkably, but renal failure progressed rapidly to end stage kidney, then hemodialysis was continued. Although subsequent 3 years uneventful maintenance hemodialysis had been performed, she admitted to our hospital again because of progressive dyspnea with hemoptysis after upper respiratory tract infection. On admission anti-MPO ab were detected again and steroid administration was started. Pulmonary hemorrhage was improved with decreased anti-MPO ab titer. While tapering the dosis of steroid, anti-MPO ab again increased and pulmonary hemorrhage recurred. Although pulse methylprednisolone therapy and plasma exchange were performed, respiratory failure progressed rapidly and she died of sepsis. Postmortem examination showed no evidence of systemic vasculitis. In this case, titer of anti-MPO ab was associated with not only idiopathic crescentic glomerulonephritis but also with pulmonary hemorrhage. We tried to detect enzymatically active MPO in serum. Titer of serum MPO was also associated with disease activity and anti-MPO ab. It is suggested that both anti-MPO ab and serum MPO are closely related to the pathogenesis of idiopathic crescentic glomerulonephritis and pulmonary hemorrhage.
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PMID:[A case of anti-myeloperoxidase antibodies-associated idiopathic crescentic glomerulonephritis with pulmonary hemorrhage]. 166 75

To determine whether plasma exchange was of additional benefit in patients treated with oral immunosuppressive drugs for focal necrotizing glomerulonephritis (without anti-GBM antibodies), we performed a randomized controlled trial with stratification for renal function on entry. Forty-eight cases were analyzed, 25 in the treatment group (plasma exchange, prednisolone, cyclophosphamide and azathioprine) and 23 in the control group (drug therapy only). There was no difference in outcome in patients presenting with serum creatinine less than 500 mumol/liter (N = 17), or greater than 500 mumol/liter but not on dialysis (N = 12), all but one of whom had improved by four weeks. However, patients who were initially dialysis-dependent (N = 19) were more likely to have recovered renal function (P = 0.041) if treated with plasma exchange as well as drugs (10 of 11) rather than with drugs alone (3 of 8). Long-term follow-up showed that improvement in renal function was generally maintained. The results of this trial confirm that focal necrotizing glomerulonephritis related to systemic vasculitis responds well to immunosuppressive drugs when treatment is started early, and suggest that plasma exchange is of additional benefit in dialysis-dependent cases.
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PMID:Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. 174 27

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

Self-tolerance is maintained by: thymic influences on developing T cells; peripheral mechanisms that can tolerise post-thymic T cells; and to a variable extent the tolerisation of potentially autoreactive B cells. The presence of autoreactive T cells in normal individuals suggests that mechanisms to control the activity of such cells may be important. Failure of any of these processes may lead to autoimmunity. The relationship between glomerulonephritis and the mechanisms leading to breakdown of self-tolerance remains elusive. An important observation is that autoimmune diseases are strongly associated with particular products of the major histocompatibility complex (MHC). This association may reflect the intimate involvement of the MHC in thymic T cell education. Another explanation is that T cells only recognise antigens presented in the context of MHC molecules. Although there has been progress in identifying the targets recognised by autoantibodies in vasculitis and anti-GBM disease, nothing is known about the T cells involved. Despite our ignorance, therapy aimed specifically at the T cell can be effective. This approach is being supplemented by attempts to engage immunoregulatory mechanisms, such as idiotype-antiidiotype interactions. The hope is that such treatments, or combinations thereof, will allow a more focused suppression of the autoimmune response, in contrast to the non-specific (and therefore potentially dangerous) methods of immunosuppression available at present.
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PMID:Autoimmunity and the pathogenesis of glomerulonephritis. 220 12

Anti-neutrophil cytoplasmic antibodies (cANCA) were detected in 3 patients with anti-glomerular basement membrane (anti-GBM) disease. All 3 cases presented late in their clinical course, with severe renal involvement and alveolar hemorrhage. Anti-neutrophil cytoplasmic antibodies were associated with clinical features outwith the lungs and kidneys; in one case cANCA were initially absent but subsequently developed concurrently with the clinical appearance of systemic vasculitis as the anti-GBM antibody titer was falling. These findings confirm that cANCA can complicate anti-GBM disease and suggest that cANCA may identify a distinct subset of patients with anti-GBM disease, supporting a pathogenic role for cANCA in the development of systemic vasculitis.
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PMID:Sequential development of systemic vasculitis with anti-neutrophil cytoplasmic antibodies complicating anti-glomerular basement membrane disease. 235 67

Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patients with renal disease, with and without systemic vasculitis, were analyzed. Of 76 patients with pauci-immune glomerulonephritis with crescents or necrosis, 87% had ANCA by IIFM (38% of C-ANCA type, 49% of P-ANCA type), and 78% had ANCA by EIA. Of 55 patients with nonlupus immune complex-mediated glomerulonephritis, only 11% had ANCA by IIFM and 5% had ANCA by EIA. Of 24 patients with anti-GBM antibody-mediated glomerulonephritis, none had ANCA. Renal and extrarenal lesions were studied in 81 patients with ANCA-associated glomerulonephritis. These patients formed a pathologic continuum ranging from renal-limited to widespread systemic vascular injury, including patients with primary crescentic glomerulonephritis, Wegener's granulomatosis, and polyarteritis nodosa. In ANCA-positive patients the frequency of C-ANCA and P-ANCA correlated with disease distribution. P-ANCA was most frequent with renal-limited disease and C-ANCA was most frequent when there was lung and sinus involvement. It is proposed that ANCA are not only useful diagnostic markers, but may also be directly involved in a novel pathogenetic mechanism that is a frequent cause of crescentic glomerulonephritis and systemic necrotizing vasculitis.
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PMID:Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. 268


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