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)

Anti-neutrophil cytoplasmic autoantibodies (ANCA) specific for constituents of neutrophil primary granules were used for enzyme immunosorbent assay in patients with vasculitic syndrome and glomerulonephritis. Proteinase 3 specific ANCA (PR3-ANCA), which include most of cytoplasmic staining pattern ANCA on indirect immunofluorescence assay (IIF) using alcohol-fixed neutrophils, were useful serologic markers for diagnosis of Wegener's granulomatosis and their titers correlated with disease activity. Myeloperoxidase specific ANCA (MPO-ANCA), which include most of perinuclear staining pattern ANCA on IIF, were detected not only in patients with well recognized clinicopathologic vasculitic syndrome and glomerulonephritis, such as microscopic polyarteritis nodosa, allergic granulomatous angitis and idiopathic crescentic necrotizing glomerulonephritis but were also detected in patients with unclassified vasculitis which are difficult to assign to a distinct diagnostic category. Patients with MPO-ANCA had common clinicopathological features, such as rapidly progressive glomerulonephritic syndrome, pulmonary hemorrhage and purpura. Histologically, patients with MPO-ANCA had focal segmental necrotizing glomerulonephritis with various degrees of crescent, pulmonary alveolar hemorrhage and leukocytoclastic vasculitis induced by necrotizing capillaries. A new clinical entity, MPO-ANCA related vasculitis in vasculitic syndrome, is proposed to manage and investigate the pathogenesis of vasculitis.
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PMID:[Anti-neutrophil cytoplasmic autoantibody (ANCA) in systemic vasculitic syndrome]. 837 2

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. All 44 patients with ANCAs had histologic evidence of this spectrum of diseases. Thirteen patients without histologic evidence of this spectrum of diseases had negative tests for ANCAs. There were no pathologic features that reliably identified patients with one or the other type of ANCA. Eighteen of 31 patients with lesions of Wegener's granulomatosis had antibodies to PR3, seven had antibodies to MPO, and six had neither. Three of four patients with necrotizing arteries without granulomas had anti-MPO antibodies, but similar lesions were seen, together with extravascular granulomas, in three patients with anti-PR3 antibodies. Of 16 patients with alveolar hemorrhage, nine had anti-PR3 and five had anti-MPO antibodies. Two patients diagnosed clinically as having Churg-Strauss syndrome had anti-MPO antibodies. In 16 of the 25 patients with ANCAs and a histologic diagnosis of Wegener's granulomatosis the diagnosis was made on the basis of extravascular granulomatous lesions alone, which argues against the requirement for vasculitis. Of six patients with negative tests for ANCAs and histologically diagnosed Wegener's granulomatosis, none had evidence of renal involvement. We conclude that in the appropriate clinical setting the presence of anti-PR3 or anti-MPO antibodies provides reliable evidence of the above spectrum of diseases, but that subclassification (to the extent this is possible) depends on the presence of distinctive clinical or pathologic features. In patients with negative tests for ANCAs, interpretation of clinical and histologic findings remains the only definitive method of diagnosis.
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PMID:Correlation of antineutrophil cytoplasmic antibodies with the extrarenal histopathology of Wegener's (pathergic) granulomatosis and related forms of vasculitis. 838 64

Wegener's autoantigen (WA), a 29 kD multifunctional protein, is the principal target antigen of autoantibodies associated with Wegener's granulomatosis (WG). WA was first identified as proteinase 3 (PR3), which is now known to be identical with myeloblastin and AGP7. Like other lysosomal proteins, WA/PR3 displays enzymatic activity, differentiation factor activity for myeloid precursor cells, and antimicrobial functions. Neutrophilic polymorphonuclear leukocytes (PMN) and a subpopulation of monocytes contain high levels of WA/PR3 in their myeloperoxidase-positive granules. The autoantibodies from WG sera produce a finely granular, centrally accentuated fluorescence pattern on PMN and monocytes and have been designated 'classic' pattern antineutrophil cytoplasmic autoantibodies (cANCA). However, PMN/monocyte activation (in vitro/ex vivo) is associated with the translocation of WA/PR3 on the cytoplasm membrane. WA/PR3 is accessible to the WG-associated autoantibody: cANCA stimulate cytokine-preactivated PMN to produce oxygen radicals and to degranulate. Furthermore, cANCA interfere with the biological functions of WA/PR3 (e.g. inhibition of elastinolytic activity). Hence, cANCA represents not only the best seromarker for WG so far available, but several lines of evidence indicate that the autoantibodies against WA/PR3 play a major role in the pathogenesis of this enigmatic disease.
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PMID:'Classic' anti-neutrophil cytoplasmic autoantibodies (cANCA), 'Wegener's autoantigen' and their immunopathogenic role in Wegener's granulomatosis. 838 90

The past decade has seen an explosion of data on the new group of autoantibodies known collectively as ANCA (anti-neutrophil cytoplasmic antibodies). ANCA are specific for granule proteins of granulocytes and monocytes and induce distinct fluorescence patterns, e.g. the cytoplasmic (classic) cANCA and the perinuclear pANCA. cANCA is induced by antibodies directed against Proteinase 3 (PR3; PR3-ANCA) in about 90% of all ANCA-positive sera, and pANCA is induced by antibodies against myeloperoxidase (MPO; MPO-ANCA) in about 40%. A further staining pattern, which does not have a clear cut association with a distinct granule protein, is sometimes seen in chronic inflammatory bowel diseases. PR3-ANCA are serological markers for Wegener's granulomatosis (WG) and MPO-ANCA are associated with certain subtypes of primary vasculitides. Evidence exists that both the autoantigen and ANCA participate in the pathogenesis of at least the group of 'ANCA-associated vasculitides'.
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PMID:ANCA and associated diseases: immunodiagnostic and pathogenetic aspects. 841 69

To determine the spectrum of systemic diseases associated with pauci-immune necrotizing crescentic glomerulonephritis, we have analysed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of antinuclear cytoplasmic antibodies (ANCA) in 40 patients selected only on renal histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24. Extra-glomerular vasculitis was seen in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis, three had a macroscopic form of polyarteritis nodosa and 17 could not be adequately classified. An additional patient had clinical signs of Wegener's granulomatosis without clinical and histological evidence of vasculitis. ANCAs were detected in 28 of 33 and 25 of 34 sera tested by immunofluorescence and enzyme-linked immunoassay, respectively: 19 contained anti-myeloperoxidase antibodies and six had anti-proteinase 3 activity. Anti-myeloperoxidase and anti-proteinase 3 antibodies were present in all clinical subgroups but with various frequencies: anti-myeloperoxidase antibodies were more common (six of 12) than anti-proteinase 3 (four of 12) in patients with suspected or histologically proven Wegener's granulomatosis. Anti-proteinase 3 antibodies were 3- to 4-fold more common in patients with Wegener's granulomatosis than in those with systemic vasculitis of other causes (one of 12) or necrotizing crescentic glomerulonephritis without evidence of extra-renal vasculitis (one of 10). These results strongly suggest that pauci-immune necrotizing crescentic glomerulonephritis belongs to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This study shows substantial improvement in renal prognosis and life expectancy with aggressive immunosuppressive therapy despite the older age of the patients, dissemination of the vasculitic process and often delayed diagnosis.
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PMID:Necrotizing crescentic glomerulonephritis without significant immune deposits: a clinical and serological study. 810 42

Recently it has been demonstrated that human antibody fragments with binding activities against self antigens can be isolated from repertoires of rearranged V genes from non-immunized humans. We have applied phage display technology to study the B cell repertoire for antibody activity against neutrophil cytoplasmic antigens. These antibodies may play an important role in Wegener's granulomatosis (WG) and related forms of vasculitides. Autoantibodies in patients with WG are directed against proteinase 3. The immunodominant antigen in other forms of vasculitis is myeloperoxidase, but the B cell response can also be directed against other neutrophil enzymes, e.g. lysozyme, human neutrophil elastase, lactoferrin and cathepsin G. We show here that anti-self reactivity against neutrophil cytoplasmic antigens can be detected in the rearranged V gene repertoire of healthy individuals and that the reactivity can be directed against structural related epitopes which are present on different neutrophil cytoplasmic antigens. The scFv with binding activities were sequenced and the V gene usage, the level of somatic mutations and the immunoserological characteristics of the antibody fragments are discussed. Further evidence is presented that antibody fragments consisting only of a heavy chain variable domain can recognize neutrophil cytoplasmic antigens in a specific manner. These single-domain antibody fragments were used in experiments designed to establish the relative role of the light chain variable domains in antigen binding.
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PMID:Molecular characteristics of anti-self antibody fragments against neutrophil cytoplasmic antigens from human V gene phage display libraries. 853 74

Many cutaneous and systemic disorders are associated with inflammation and necrosis of blood vessels. Several classifications of vasculitis have been used. Internists tend to utilize the classification of Fauci with modifications such as those by Cupps. Gibson and Ryan, who are dermatopathologists, have classified vasculitis based on vessel size, leukocyte type, and presence of granulomas. A more recent classification has been developed by Jennette, a pathologist, and colleagues. The etiology of vasculitis is varied; it includes bacteria, viruses, chemicals, autoimmune disease, malignancy and abnormal exogenous and endogenous proteins. Leukocytoclastic vasculitis can be experimentally reproduced by the Arthus phenomenon. IgM and C3 are found in cutaneous blood vessels and associated with circulating immune complexes. CH50, C3 and C4 may be reduced in serum. Increased incidence of nasal carriage of staphylococci is associated with higher relapse rates in Wegener's granulomatosis and toxic shock syndrome toxin from staphylococci is associated with the Kawasaki syndrome. Additionally, at least four systemic vasculitic drug reactions can be confirmed with patch testing. Antineutrophil cytoplasmic antibodies (ANCA) are found in association with certain systemic vasculitides. These may be tested with indirect immunofluorescence and enzyme linked immunosorbent assays (ELISA) with radioimmunoassays. Originally cytoplasmic ANCA (cANCA) was identified with proteinase 3 as the antigen and perinuclear ANCA (pANCA) was related to myeloperoxidase. While cANCA is very specific for proteinase 3, pANCA is associated with a number of antigens other than myeloperoxidase. pANCA is found with alcohol fixed but not formalin-fixed neutrophils. cANCA is particularly sensitive and specific for Wegener's granulomatosis and predicts prognosis and response to therapy. pANCA is not so specific and is associated with a number of other vasculitic syndromes. Cutaneous vasculitis is managed primarily with colchicine, dapsone and prednisone, with recent studies indicating that there may be a synergistic effect of pentoxifylline with dapsone. Systemic vasculitis involves treatment with various agents. Recently it has been observed that co-trimoxazole (trimethoprim/sulfamethoxazole) is useful in many cases of Wegener's granulomatosis along with other more toxic chemotherapeutic agents.
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PMID:Vasculitis. 855 52

ANCA-associated vasculitides (AAV) include primary vasculitides that affect predominantly small vessels such as Wegener's Granulomatosis (WG), Microscopic Polyangiitis (MPA) and Churg-Strauss Syndrome (CSS). The former is closely associated with cANCA, induced by proteinase 3, MPA is characterized by pANCA with MPO specificity and the latter, CSS, can--to a far lesser extent--be associated with, either c- or pANCA. All AAV have in common (as opposed to immune-complex-vasculitides) that they occur without complement consumption and show histologically no deposition of immune complexes (pauci-immune vasculitis). Clinically, the AAV show quite variable courses. The mostly clinically rather inapparent initial phase, which is typically granulomatous in WG and CSS, is mostly followed by a potentially life-threatening phase of full blown generalized systemic vasculitis. Frequently, rheumatic complaints are the initial symptom. The characteristic clinical features in the full blown generalized vasculitis are mostly found in the upper respiratory tract, the lung and/or the kidney. Subsequently, the clinical pictures of AAV will be described, especially taking into consideration the rheumatic manifestations as early symptoms. Furthermore, pathodynamics and differential diagnoses of AAV will be regarded.
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PMID:[ANCA-associated vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis). 1. Systemic aspects, pathogenesis and clinical aspects]. 857 83

This article summarizes the most recent findings concerning the clinical relevance of antineutrophil cytoplasmic autoantibody (ANCA) testing for patients with idiopathic vasculitis and with diseases known to be associated with secondary vasculitis. The clinical value of granular cytoplasmic pattern (c)ANCA (proteinase 3 [PR3]-ANCA) and perinuclear fluorescence pattern (p)ANCA (myeloperoxidase [MPO]-ANCA) testing in Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA), respectively, is now well established; however, the various subspecificities beside myeloperoxidase (MPO), which also include the perinuclear staining pattern, are detectable not only in vasculitis, but equally in a heterogeneous patient population with a spectrum of autoimmune diseases and idiopathic chronic inflammatory diseases of the bowel, liver, and so forth. Future studies must establish the specificity, sensitivity, and role of these pANCA subspecificities usually measured by enzyme-linked immunosorbent assays for distinct disease entities in clinical medicine. In summary, despite the relatively poor understanding of the immunopathogenesis of ANCA-associated disease, cANCA (PR3-ANCA) and pANCA (MPO-ANCA) continue to be important clinical markers of the so-called "ANCA-associated vasculitides" (i.e., WG, MPA, and Churg-Strauss syndrome).
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PMID:Antineutrophil cytoplasmic autoantibody testing in vasculitides. 859 45

Proteinase 3 (PR3) is a multifunctional serine protease found in myeloperoxidase-positive granula of PMN. It is also the main target antigen for antineutrophil cytoplasmic antibodies (ANCA) found in Wegener's granulomatosis (WG). There is ample evidence that these autoantibodies play an active role in the pathogenesis of this disease. We have established the expression of the autoantigen (PR3) in a baculovirus expression system using insect cells. Recombinant PR3 was identified by IIF, direct ELISA using 3 different MoAbs and by catching ELISA using a MoAb and a rat polyclonal Ab or cANCA-positive WG patient sera. As purification of human PR3 from blood-derived PMNs has been shown to be difficult and very inefficient, insect cell-derived recombinant PR3 offers new possibilities for obtaining sufficient amounts of this protein to facilitate further biochemical characterizations.
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PMID:Expression of the human autoantigen of Wegener's granulomatosis (PR3) in a baculovirus expression system. 860 78


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