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)

Antineutrophil cytoplasmic autoantibodies (ANCAs) are found in the sera of patients with systemic vasculitis and crescentic glomerulonephritis. We developed monoclonal antibodies against myeloperoxidase (MPO), which is a major perinuclear-ANCA antigen, and examined the presence of MPO in renal tissue from patients with rapidly progressive glomerulonephritis (RPGN) using these monoclonal antibodies. Myeloperoxidase was found in the glomeruli in four of five cases of perinuclear ANCA-positive RPGN, and the distribution pattern was different from that of immunoglobulin G. In perinuclear ANCA-negative crescentic glomerulonephritis, MPO also was detected in two of three cases. Myeloperoxidase was not detected in the capillary walls or mesangium in other nephropathies, such as minimal change disease, membranous nephropathy, and mesangial proliferative glomerulonephritis, or in normal controls. Myeloperoxidase activity was elevated and inversely correlated with the titer of MPO-ANCAs in the sera of perinuclear ANCA-associated RPGN. These data suggest that MPO plays an important role in the glomerular injury of RPGN.
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PMID:Significance of myeloperoxidase in rapidly progressive glomerulonephritis. 761 Dec 43

A retrospective analysis of the authors' own findings and foreign authors' data has demonstrated that neutrophilic cytoplasm antibodies (NCAs) play a definite pathogenetic role in the activation of neutrophils, a central link in the pathogenesis of vascular wall damage in necrotizing vasculitides. The clinical value of NCAs varies with their specificity. Proteinase 3 antibodies whose detection allows one to suppose Wegener's granulomatosis are of greater diagnostic value. Myeloperoxidase antibodies are revealed in various necrotizing vasculitides and promptly progressive glomerulonephritis and more infrequently in other diseases. Thus, the detection of antibodies to proteinase-3 and myeloperoxidase in the presence of appropriate clinical signs is most likely to diagnose primary necrotizing vasculitis. The changes in the levels of NCA reflect the activity of a renal processes and the progression of the whole disease.
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PMID:[Clinical and pathogenetic aspects of kidney damage associated with neutrophilic cytoplasm antibodies]. 762 83

Detection of circulating antineutrophil cytoplasmic antibodies (ANCA) to the neutrophil serine proteinase, proteinase 3 (PR3), has proven valuable for the diagnosis of Wegener's granulomatosis (WG). However, the importance of these autoantibodies in the pathogenesis of WG remains unknown. It was recently reported that anti-PR3 autoantibodies (PR3-ANCA) from some patients with WG inhibit the proteolytic activity of PR3 and interfere with the inactivation of PR3 by the physiologic inhibitor, alpha 1-proteinase inhibitor (alpha 1-PI). We have studied the effect of PR3-ANCA on the enzymatic activity of PR3 and its correlation with disease activity in patients with WG. We purified IgG from 21 PR3-ANCA positive sera obtained from 17 patients with WG, and determined its effect on the esterolytic and proteolytic activity of purified human PR3 using Boc-Ala-O-Nitrophenyl ester and fluoresceinated-elastin as enzyme substrates. Controls included seven sera containing anti-MPO autoantibodies (MPO-ANCA) from patients with systemic vasculitis and seven ANCA-negative sera obtained from healthy individuals. We found that PR3-ANCA from 9 of the 17 patients significantly inhibited the activity of PR3. There was no correlation between the titers of PR3-ANCA and their inhibitory activity. For one extensively characterized autoantibody, the inhibition reached 70 to 95% at 20-fold molar excess of IgG to enzyme, with an apparent Kiapp of 56.5 microM. This inhibition was non-competitive in nature, and was additive to that produced by alpha 1-PI. A review of the clinical histories of the patients revealed a strong association between active WG and inhibitory autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of proteinase 3 by ANCA and its correlation with disease activity in Wegener's granulomatosis. 764 21

Antimyeloperoxidase autoantibodies are found in the sera of some patients with glomerulonephritis and systemic vasculitis. Previously, we demonstrated that they were able to stimulate neutrophils to damage cultured human endothelial cells. We now report that antimyeloperoxidase antibodies are able to stimulate neutrophils to adhere to cultured human endothelial cells. Immunoglobulin G purified from myeloperoxidase-antineutrophil cytoplasmic autoantibody positive sera increased adherence to 331 +/- 60% of unstimulated controls. In a similar manner, rabbit antimyeloperoxidase enhanced neutrophil adherence. Stimulating the endothelial cells with 10 micrograms/mL endotoxin enhanced antimyeloperoxidase stimulated adherence. In the presence of a CD18 blocking antibody (MoAb 60.3), antimyeloperoxidase-stimulated adherence was significantly decreased. These results add further understanding to the antimyeloperoxidase-stimulated neutrophil-endothelial cell interaction and further support the hypothesis that antimyeloperoxidase autoantibodies are of pathogenic import in glomerulonephritis and vasculitis.
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PMID:Antimyeloperoxidase antibodies induce neutrophil adherence to cultured human endothelial cells. 764 63

Antineutrophil cytoplasmic antibodies (ANCA) are a heterogeneous group of autoantibodies with a wide and diverse range of clinical associations. In vasculitis, the diagnostic utility of proteinase 3 (PR3)-ANCA and myeloperoxidase-ANCA for Wegener's granulomatosis and microscopic polyangiitis, respectively, is now well established. Because of their significance as tools for diagnosis and prognosis, these autoantibodies have been analyzed extensively as markers for underlying immunopathogenic disturbances. In this review, we consider recent advances in the understanding of ANCA, focusing on their detection, diagnostic value, and role in the pathogenesis of vasculitis. In addition, promising new ways have been developed to elucidate the pathophysiologic and diagnostic relevance of the ANCA target antigens PR3 and myeloperoxidase. A great deal of attention and controversy has focused on the possible mechanisms underlying the ANCA-related immune response, such as antigenic cross-reactivity between human polymorphonuclear leukocyte proteins and extrinsic antigens by molecular mimicry, idiotype network regulation, and T cell reactivity to PR3 and myeloperoxidase.
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PMID:Immunodiagnostic and pathophysiologic aspects of antineutrophil cytoplasmic antibodies in vasculitis. 771 17

Anti-neutrophil cytoplasmic antibodies (ANCA) are a heterogeneous group of autoantibodies with a wide and diverse range of clinical associations. Over the past decade ANCA have been the subject of extensive investigations. In vasculitis the diagnostic utility of proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA), respectively, is now well established. Because of their significance as tools for diagnosis and prognosis of "ANCA-associated vasculitides," these autoantibodies have been analyzed extensively as markers for underlying immunopathogenic disturbances. Data regarding the detection of ANCA and their diagnostic value and role in the pathogenesis of rheumatic disorders will be discussed in this review. Growing evidence points to a pathophysiologic and diagnostic relevance of the ANCA target antigens PR3 and MPO. To date, there is mounting evidence that ANCA can have pathophysiologic effects on neutrophils, and may play a direct role in ANCA-associated vasculitides. A pathogenic model for ANCA-mediated vasculitis will be presented in this paper.
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PMID:[Antineutrophilic cytoplasmic antibodies (ANCA) in inflammatory rheumatic diseases: immunodiagnostic and immunopathogenetic aspects]. 772 5

A 42-year-old female with progressive systemic sclerosis (PSS) developed rapidly progressive renal insufficiency. Renal pathology revealed crescentic glomerulonephritis (CrGN) without mucoid intimal proliferation of the interlobular arteries and fibrinoid necrosis of the afferent arterioles. Immunofluorescent micrography showed linear deposition of IgG along the glomerular capillary wall. Not only anti-glomerular basement membrane antibody (anti-GBM Ab), but also myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were simultaneously detected by an enzymelinked immunosorbent assay (ELISA). She did not develop pulmonary hemorrhage. These findings were compatible with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation of serum creatinine level (over 6.0mg/dl), a high titer of MPO-ANCA (660.7 ELISA unit/ml) and anti-GBM Ab (409 units). Therefore, she was started on methylprednisolone pulse therapy and temporary hemodialysis. After immunosuppressive therapy, both antibodies titers had fallen to within the normal range. However, end-stage renal failure did not improve and maintenance hemodialysis was introduced. Recently, six patients of PSS with MPO-ANCA were first reported in Japan. These autoantibodies detected in this case strongly suggested that there may be associations between anti-GBM Ab nephritis and ANCA-related vasculitis and PSS.
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PMID:[A case of progressive systemic sclerosis with crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) and anti-glomerular basement membrane antibody (anti-GBM Ab)]. 773 Nov 10

Previous studies have shown a number of different associations between major histocompatibility complex (MHC) alleles and primary systemic vasculitis. Disease heterogeneity and the lack of specificity of certain MHC typing techniques may have contributed to the lack of consistency in those studies. We therefore studied a relatively homogeneous group of 94 patients with Wegener's granulomatosis, microscopic polyangiitis, or renal-limited vasculitis using molecular techniques that allow more precise assignment of MHC genotype. DNA was prepared from peripheral blood and DRB1 genotype determined by Taq restriction fragment length polymorphism. DQB1 and DPB1 genotype were assigned by polymerase chain reaction amplification followed by probing with allele-specific oligonucleotides. Specificity of associated anti-neutrophil cytoplasm antibodies (ANCA) was determined where possible by solid phase immunoassays using purified proteinase 3 (PR3) and myeloperoxidase (MPO). After correction for multiple comparisons there were no significant differences in the distribution of DRB1, DQB1 and DPB1 alleles between a local control group (N = 90 for DRB1, N = 50 for DQB1 and DPB1) and the patient group as a whole (N = 94) or two a priori defined subgroups (anti-PR3 positive, N = 35; anti-MPO positive, N = 22). We have therefore found no significant association between primary systemic vasculitis and any MHC class II allele. This, together with the fact that previous smaller studies have shown no consistent association, suggests that any such association is very weak, if it exists at all.
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PMID:Distribution of MHC class II alleles in primary systemic vasculitis. 773 Nov 60

Antineutrophil cytoplasmic antibodies (ANCA) encompass a heterogeneous group of autoantibodies targeting antigens in neutrophils (PMN), monocytes, and endothelial cells. ANCA are routinely detected by the indirect immunofluorescence technique (IFT) and at least three different patterns of fluorescence can be distinguished which have been assigned the acronyms cANCA, pANCA and aANCA. cANCA is mostly induced by proteinase 3 (PR3) antibodies (PR3-ANCA), and pANCA by myeloperoxidase (MPO) antibodies (MPO-ANCA), while aANCA has unidentified subspecificity. Over the past decade, ANCA have been the subject of extensive investigation. They have proved to be of significant value both as diagnostic tools and for follow-up in several forms of systemic vasculitis (e.g. Wegener's granulomatosis, WG; microscopic polyarteritis, MPA; Churg-Strauss syndrome, CSS) which are now termed 'ANCA-associated vasculitides'. Furthermore, it is suspected that the presence of ANCA is an important factor in the pathogenesis of these disease groups. Data regarding the detection of ANCA and their diagnostic value and role in the pathogenesis of vasculitic disorders will be discussed in this review. Growing evidence points to a pathophysiological and diagnostic relevance of the distribution of the ANCA target antigens PR3 and MPO (presence in the circulation, on cell membranes, and in tissue extracellularly). An autoimmune process has been implicated in the pathogenesis of ANCA-associated vasculitis, but it is uncertain which mechanism underlies the induction of the ANCA-related immunoresponse. In this paper mechanisms such as antigenic cross-reactivity between human PMN proteins and extrinsic antigens by molecular mimicry, idiotypic immunoglobulin regulation, and T-cell reactivity to PR3 and MPO will be discussed.
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PMID:Antineutrophil cytoplasmic autoantibodies, autoantigens, and systemic vasculitis. 774 41

During a seven-year period (1986-1992) 719 adults (age > 16 years) underwent diagnostic renal biopsy in Stockholm (adult population 1.2 million). Seventy-one (10%) new cases of pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) with or without systemic vasculitis were found: 39 females and 32 males (median age 67, range 20-84 years). The mean yearly incidence for the whole period was 0.8/100,000 population. The yearly incidence doubled from 0.6 before to 1.2/100,000 population after 1990. The incidence was highest among those > 65 years of age. Age-corrected incidences for this age group increased from 1.4 before to 3.9/100,000 after 1990. Anti-neutrophil cytoplasmic antibodies (ANCAs) tested in 60, showed antibodies against proteinase 3 (PR3) in 29 patients, against myeloperoxidase (MPO) in 26 and none in five patients. Mortality was highest in the early stages of the disease. From a total of 11 patients, 7 (15%) died within 2.5 months of diagnosis. Forty-six out of all 71 patients with NCGN belonged to the catchment area of our clinic and were studied in more detail. Twenty-six had microscopic polyangiitis (ANCAs were analyzed in 24, of these 16 had anti-MPO, 6 anti-PR3, 2 had none), 13 had Wegener's granulomatosis (ANCAs were analyzed in all, of these 12 had anti-PR3, 1 anti-MPO) and seven had disease limited to the kidneys (ANCAs were analyzed in 6, 5 had anti-MPO, one was negative). At the time of diagnosis, 16 patients had s-creatinine < 300 mumol/l while 14 patients were dialysis-dependent (seven only temporarily). All patients received immunosuppressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Incidence and outcome of pauci-immune necrotizing and crescentic glomerulonephritis in adults. 777 68


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