Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

alpha 1-antitrypsin (alpha 1-AT) is a naturally occurring inhibitor of proteinase 3 (PR3) and elastase, two of the target antigens of anti-neutrophil cytoplasmic antibodies (ANCA). An increased incidence of alpha 1-AT phenotypes associated with dysfunctional alpha 1-AT or low serum levels has been reported in patients with anti-PR3 antibodies. We have studied the relationship between ANCA, and phenotypes and serum levels of alpha 1-AT. Phenotypes usually associated with a moderate or severe reduction in alpha 1-AT serum levels or in dysfunctional activity were found more often in individuals with anti-PR3 antibodies than in the general population: four of the 31 patients (13%) with anti-PR3 antibodies had phenotypes MZ (n = 2), S (n = 1) or Z (n = 1) (P < 0.05). However, the corresponding alpha 1-AT serum levels were normal (n = 3) or elevated (n = 1). None of the 31 sera with anti-PR3 antibodies had low levels of alpha 1-AT. No abnormal alpha 1-AT phenotype was demonstrated in seven patients with anti-elastase antibodies, despite a low level of alpha 1-AT in one serum. Anti-myeloperoxidase antibodies are common in patients with ANCA, but no abnormal phenotype or low serum alpha 1-AT level was demonstrated in any of 29 sera containing these antibodies. Finally anti-glomerular basement membrane (GBM) antibodies occur occasionally in patients with ANCA-associated diseases, but again none of 10 sera had an abnormal alpha 1-AT phenotype or low serum level. ANCA were not demonstrated by indirect immunofluorescence in any serum from 73 patients with abnormal alpha 1-AT phenotypes. These results confirm that patients with anti-PR3 antibodies often have alpha 1-AT phenotypes that are usually associated with low serum levels of alpha 1-AT or with dysfunctional protein. Nevertheless, the incidence of anti-PR3 antibodies in patients with abnormal alpha 1-AT phenotypes is very low. This probably reflects the rarity of Wegener's granulomatosis, the major disease associated with anti-PR3 antibodies, and the relative frequency of abnormal alpha 1-AT phenotypes. The mechanism for the development of anti-PR3 antibodies in patients with abnormal alpha 1-AT phenotypes is not clear, but may relate to the increased propensity of unbound and uninhibited PR3 to stimulate autoantibody production.
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PMID:Alpha 1-antitrypsin deficiency and anti-proteinase 3 antibodies in anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis. 774 54

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

Anti-neutrophil cytoplasmic antibodies (ANCA) constitute a new group of antibodies that are directed against myeloid proteins. Several antigens recognized by ANCA have been described. Antibodies directed to proteinase 3, myeloperoxidase and/or elastase are closely associated with necrotizing systemic vasculitis and/or necrotizing and crescentic glomerulonephritis. Changes in levels of anti-proteinase 3 in generally reflect disease activity in Wegener's granulomatosis. The diagnostic significance of other or still unknown specificities has not yet been definitely established. Recent data from in vitro and in vivo models suggest a role for ANCA in the pathogenesis of systemic vasculitides and/or necrotising and crescentic glomerulonephritis.
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PMID:Anti-neutrophil cytoplasmic antibodies: a new class of autoantibodies in glomerulonephritis, vasculitis and other inflammatory disorders. 783 42

Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies mainly directed against alpha granules' components (especially proteinase 3 (PR 3) and myeloperoxidase (MPO). They are usually detected by indirect immunofluorescence (IIF) giving essentially two staining patterns, cytoplasmic and perinuclear. Nevertheless the IIF method does not allow to precise the true specificity of ANCA. From now on a better classification of systemic vasculitis requires such a determination. This can be done only by solid phase tests that require to be reliable, highly purified antigen, and, from a practical point of view, only a MPO-ELISA is currently available. We report on our experience with Western blot analysis of 67 IIF-ANCA positive sera. Using Western blot analysis to characterize ANCA specificity is not so easy as in the case of antibodies directed against extractable nuclear antigens: only PR 3 ANCA detection could be done reproducibly. PR 3 ANCA are mainly detected in the c-ACPN positive sera of patients with Wegener's granylomatosis. Nevertheless using both MPO-ELISA and PR 3 blot seems to increase the frequency of serum containing the two types of ANCA (anti PR 3 and anti MPO).
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PMID:[Detection of anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity by immunoblotting]. 785 57

Renal vasculitis frequently presents itself as rapidly progressive glomerulonephritis, but its diagnosis may be hampered by the difficulty in demonstrating classic vasculitic lesions in renal biopsy specimens. Early diagnosis of renal vasculitis has been greatly enhanced by the advent of antineutrophil cytoplasmic autoantibodies (ANCA). On indirect immunofluorescence microscopy, cytoplasmic ANCA (C-ANCA) show cytoplasmic staining of alcohol-fixed neutrophils and are directed against proteinase 3 in the primary granules of neutrophils. Perinuclear ANCA (P-ANCA) show perinuclear staining due to redistribution of granular antigens, and are specific for myeloperoxidase in the primary granules of the vasculitic patients. C-ANCA are most frequently associated with Wegener's granulomatosis and P-ANCA, with "idiopathic" necrotizing and crescentic glomerulonephritis (renal-limited disease). Patients with microscopic polyarteritis may be associated with either P-ANCA or C-ANCA and there is a considerable overlap between Wegener's granulomatosis and microscopic polyarteritis in both clinical features and serologic patterns. ANCA are not only the markers for vasculitis but may also play a role in the pathogenesis by activating the neutrophils to attack target blood vessels. There is also a crude correlation between ANCA titer and the activity of vasculitis. ANCA-associated vasculitis responds well to steroid and/or cyclophosphamide therapy. Renal failure in these patients is frequently reversible if treated early. Long-term patient and kidney survival rates are good with proper treatment and are far better than those of the other causes of rapidly progressive glomerulonephritis. Potential morbidity of steroid and immunosuppressive therapy should be reduced by the use of low effective doses and by close clinical observation and management.
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PMID:Antineutrophil cytoplasmic autoantibody--associated glomerulonephritis: potentially reversible disease. 786 52

If testing of ethanol-fixed neutrophils remains the most commonly used method to screen for ANCA. C-ANCA is highly sensitive and specific for Wegener's granulomatosis if strict criteria in defining this IF pattern are followed. P-ANCA is not specific for MPO-ANCA, when used as a screening test. Because of the increasing recognition of atypical cytoplasmic staining patterns and the lack of specificity of nuclear staining of neutrophils for MPO-ANCA, confirmatory testing by ELISA is advisable in all cases of atypical neutrophil cytoplasmic staining and in all cases of neutrophil nuclear or perinuclear staining.
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PMID:Antineutrophil cytoplasmic autoantibodies in the immunodiagnosis of systemic necrotizing vasculitis. 786 72


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