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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 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.
...
PMID:[Clinical investigation of anti-myeloperoxidase antibodies in patients with glomerulonephritis with crescent formation]. 196 27
Antineutrophil cytoplasmic autoantibodies (ANCA) are specific for constituents of neutrophil primary granules and monocyte lysosomes. There are different types of ANCA with different specificities. By indirect immunofluorescence microscopy using alcohol-fixed neutrophils as substrate, two major categories of ANCA can be recognized, one with cytoplasmic staining (C-ANCA) and the other with artifactual perinuclear staining (P-ANCA). Some C-ANCA have specificity for proteinase 3 (PR3-ANCA) and some P-ANCA have specificity for
myeloperoxidase
(
MPO
-ANCA), but there are additional C-ANCA and P-ANCA specificities. ANCA are found in the blood of patients with necrotizing systemic vasculitis, such as
Wegener's granulomatosis
and polyarteritis nodosa, and patients with idiopathic crescentic glomerulonephritis. The glomerular lesion in patients with systemic and renal-limited ANCA-associated diseases is the same, ie, a pauci-immune necrotizing and crescentic glomerulonephritis. No matter where the vascular lesions of ANCA-associated disease are (eg, kidney, lung, gut, muscle, skin), they are characterized by necrotizing inflammation and a paucity of immune deposits. The distribution of disease correlates to a degree with the ANCA specificity, although there is substantial overlap. For example, patients with
Wegener's granulomatosis
most often have C-ANCA and patients with renal-limited disease most often have P-ANCA. In patients with P-ANCA-associated glomerulonephritis, approximately 90% of the P-ANCA have specificity for
MPO
. The clinical manifestations of ANCA-associated diseases often begin following a flu-like illness. The onset is most often in the winter and least often in the summer. The renal disease usually presents as rapidly progressive renal failure with nephritis. One of the most life-threatening components of the systemic involvement is pulmonary hemorrhage caused by a necrotizing alveolar capillaritis. Intravenous cyclophosphamide plus steroids is as effective as oral cyclophosphamide plus steroids for controlling ANCA-associated diseases. Using life-table analysis, the 2-year patient and renal survival rate in both patients with renal-limited and systemic disease is greater than 70%. There is evidence that in addition to being a useful serologic marker, ANCA are directly involved in the pathogenesis of the vascular injury in patients with ANCA-associated diseases. Although ANCA antigens are normally in the cytoplasm of neutrophils and monocytes, priming of these cells, as occurs following exposure to certain cytokines, results in the release of small amounts of ANCA antigens at the cell surface. In vitro, ANCA-IgG causes cytokine-primed neutrophils to undergo a respiratory burst and degranulation.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Antineutrophil cytoplasmic autoantibodies and associated diseases: a review. 197 31
Antibodies that are directed against cytoplasmic constituents of neutrophils and monocytes (anti-neutrophil cytoplasm antibodies, ANCA) have been described in
Wegener's granulomatosis
, microscopic polyarteritis (MPA) and some cases of segmental necrotizing glomerulonephritis (SNGN). Other antibodies occasionally described in
Wegener's granulomatosis
and MPA include anti-nuclear antibodies (ANA) and anti-glomerular basement membrane (GBM) antibodies. We have studied the diversity of the corresponding antigens in ANCA-associated renal diseases. Sera from 46 patients with active histologically proven
Wegener's granulomatosis
, MPA and SNGN were tested for ANCA by indirect immunofluorescent examination of normal peripheral blood neutrophils. Thirty-four sera (74%) were positive; 16 were associated with diffuse cytoplasmic staining (cANCA) and 18 with perinuclear staining (pANCA). In addition, five demonstrated antineutrophil-specific nuclear staining (ANNA). On Western blotting of the neutrophil extract, five sera recognized a 29-kD molecule recently identified as neutrophil proteinase 3. Two sera with typical cANCA bound to molecules of 36, 38 and 116 kD and another to a molecule of 22 kD. The final serum associated with pANCA bound to a molecule of about 12 kD. Thirteen sera out of 46 (28%) tested in an ELISA contained anti-
myeloperoxidase
antibodies; 10 of these were associated with pANCA and two others with ANNA. Three sera of 17 (18%) tested contained anti-elastase antibodies; these also contained anti-
myeloperoxidase
antibodies and were associated with pANCA. However, eight sera with pANCA were negative for anti-
myeloperoxidase
antibodies and three of these were also negative for anti-elastase antibodies, suggesting further unidentified target antigen or antigens associated with the pANCA. Fifteen of the 34 sera positive for ANCA also demonstrated anti-nuclear staining on Hep-2 cells (53%) in a speckled, homogeneous, or nucleolar pattern. ANA were significantly associated with the presence of pANCA (P less than 0.01), and levels of ANA and ANCA fell in parallel after treatment. One serum with a pANCA was also positive for anti-GBM antibodies. Inhibition studies using ELISAs for anti-GBM antibodies indicated that there was no cross-reactivity between target molecules recognized by these antibodies. The diversity of target molecules recognized by ANCA suggests that cross-reactivity with bacterial structures is less likely as the primary aetiological event in the development of these antibodies than tissue destruction; and that cross-reactivity with vascular endothelium is also unlikely as the pathogenetic basis of vessel disease.
...
PMID:Diverse target antigens recognized by circulating antibodies in anti-neutrophil cytoplasm antibody-associated renal vasculitides. 197 2
Anti-neutrophil cytosolic antibodies (ANCA) and anti-endothelial cell antibodies (AECA) have been identified in a wide variety of disorders, but their pathophysiological role remains unclear. ANCA appear to be particularly associated with various forms of vasculitis including
Wegener's granulomatosis
. Kawasaki disease and microscopic polyarteritis. Cytoplasmic staining (cANCA) on indirect immunofluorescence is associated with extrarenal disease and a perinuclear pattern (pANCA) with renal limited disease. The cANCA antigen appears to be proteinase 3 and that for pANCA
myeloperoxidase
. AECA have been detected in systemic lupus erythematosus, scleroderma and dermatomyositis but are also found in systemic vasculitis, Kawasaki disease, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura and renal allograft recipients at the time of rejection. Their presence appears to be correlated with disease activity and they may be directed against epitopes on as yet unidentified infective agents that precipitate some of the diseases in which they are found that cross-react with antigenic sites exposed on endothelial cells. Measurement of these antibodies has a diagnostic role, facilitates monitoring of disease activity and may prove valuable in understanding the pathogenesis of the diseases in which they are found.
...
PMID:Anti-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies. 203 46
Sera of 64 patients with chronic inflammatory bowel disease (IBD) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) using an indirect immunofluorescence technique on ethanol-fixed human neutrophil granulocytes. 20 of 34 sera (59%) from patients with ulcerative colitis (UC) produced a fine-granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typical diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA, synonym ACPA) seen in active
Wegener's granulomatosis
(WG). The majority of the 20 p-ANCA positive UC patients had a high inflammatory disease activity. Among the 14 p-ANCA negative UC patients nine were without steroids; five of them had active disease, two were inactive and two had previously undergone colectomy. The remaining five patients still had active disease but received steroids for more than 4 weeks. Only 3 of the 30 sera from patients with Crohn's disease (CD) showed positive p-ANCA reactions. To narrow the specificity of the p-ANCA reaction all 64 sera were tested by ELISA for antibodies against anti-proteinase-3 (WG specific) and on HEp-2 cells for antinuclear (ANA) and anticytoplasmic antibodies. Ten p-ANCA positive UC sera were also tested in a
myeloperoxidase
ELISA. Only one UC serum reacted positively in the proteinase-3-ELISA and another one produced a weakly positive anti-nucleolar ANA fluorescence on HEp-2 cells. None of the tested sera reacted with
myeloperoxidase
suggesting that the p-ANCA staining pattern of granulocytes is not restricted to anti-
myeloperoxidase
antibodies as reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. 209 8
Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated with active
Wegener's granulomatosis
are directed against a soluble 29-Kd protein present in human neutrophils and monocytes. Affinity labeling with tritiated diisopropylfluorophosphate (3H-DFP) suggested that ANCA-antigen is a serine protease. We used immunoelectron microscopy to study the in situ localization of the ANCA-antigen in normal human neutrophils and monocytes using immunoglobulin G (IgG) from ANCA-positive patients and a mouse monoclonal antibody against the ANCA-antigen. Label was observed on the large granules of the neutrophils and in granules of monocytes. Double-labeling, using anti-
myeloperoxidase
or the
peroxidase
reaction as markers for azurophil granules and anti-lactoferrin as marker for specific granules, showed that ANCA is colocalized with markers of azurophil granules but not with lactoferrin. Furthermore, elastase and cathepsin G were found in the azurophil granules of neutrophils and in the
peroxidase
-positive granules of monocytes, colocalized with ANCA-antigen. Cytochalasin-B-treated neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) formed large intracellular vacuoles and were partially degranulated. Some vacuoles contained ANCA-antigen, as well as
myeloperoxidase
, elastase, and cathepsin G, demonstrating release of these enzymes from the azurophil granules into vacuoles. Our results demonstrate that ANCA-antigen is located in
myeloperoxidase
-containing granules of neutrophils and monocytes, and is packaged in the same granules as elastase and cathepsin G, the two previously identified serine proteases of myeloid leukocytes.
...
PMID:In situ localization by double-labeling immunoelectron microscopy of anti-neutrophil cytoplasmic autoantibodies in neutrophils and monocytes. 215 32
An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of circulating anti-neutrophil cytoplasm antibodies (ANCA), which are defined by a diffuse, granular staining of the cytoplasm of alcohol-fixed human neutrophils by indirect immunofluorescence (IIF). Detection of antineutrophil cytoplasm antibodies has a high sensitivity and specificity for active
Wegener's granulomatosis
(WG) and reflects the effect of treatment. In the present enzyme-linked assay, immunoplates were coated with the cytoplasmic alpha fraction of neutrophils obtained from apparently healthy human donors by nitrogen bomb cavitation and subsequent Percoll gradient centrifugation. Alkaline phosphatase-labelled anti-human IgG was used as a secondary antibody. Diluted sera from 70 patients with WG and 16 patients with other diseases with anti-
myeloperoxidase
antibodies (anti-MPO) were examined. It is concluded that the ELISA accurately detects IIF ANCA positive patients with WG, is helpful in detecting WG patients in remission, is not influenced by the presence of anti-
MPO
and may help in detecting ANCA in cases with granulocyte-specific anti-nuclear antibodies since this IIF pattern obscures the IIF ANCA patterns. The ELISA with titration can be carried out in 3.5 h whereas a rapid test just to detect ANCA can be performed in 30 min.
...
PMID:An ELISA for the detection of anti-neutrophil cytoplasm antibodies (ANCA). 215 37
Antineutrophil cytoplasmic autoantibodies with specificity for
myeloperoxidase
(
MPO
) were found in 53 patient sera that were routinely submitted for antineutrophil cytoplasmic antibody determination. Based on clinical and histologic criteria, 15 of these 53 patients were classified as having systemic necrotizing vasculitis of the polyarteritis group, 11 patients were classified as having
Wegener's granulomatosis
(WG), and 14 were classified as having idiopathic crescentic glomerulonephritis. The remaining 13 patients did not fulfill the diagnostic criteria for these disorders, although most of these patients had clinical symptoms compatible with these disorders. While all patients with WG had renal involvement, only 4 of the 15 patients with systemic necrotizing vasculitis of the polyarteritis group had glomerulonephritis. The sensitivity of autoantibodies to
MPO
for either systemic necrotizing vasculitis of the polyarteritis group, WG, or idiopathic crescentic glomerulonephritis was further tested in all our patients with these disorders (n = 104). Twenty-seven of 104 patients had autoantibodies to
MPO
. Furthermore, 69 of the remaining 77 patients had autoantibodies specific for the 29-kd serine protease, which has been reported to be specifically associated with WG. Sera from 8 patients were negative for either of these antibodies (92% sensitivity of autoantibodies to
MPO
and/or the 29-kd serine protease). The specificity of autoantibodies to
MPO
for either systemic necrotizing vasculitis of the polyarteritis group, WG, or idiopathic crescentic glomerulonephritis was also tested in selected groups of patients who had closely related diseases. Two of 144 patients had autoantibodies to
MPO
(specificity 99%).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Association of autoantibodies to myeloperoxidase with different forms of vasculitis. 165 Feb 23
The sera of 64 patients with extracapillary glomerulonephritis were investigated by enzyme-linked immunosorbent assay for the presence of antibody to human neutrophil
myeloperoxidase
(
MPO
). In all, circulating anti-
MPO
were found in 30% and antineutrophil cytoplasm antibodies (ANCA) detected by indirect immunofluorescence in 44% of the patients. Autoantibody to components of neutrophil granulocytes was not found in patients with other forms of glomerulonephritis. The incidence of ANCA (16/23) was higher than that of anti-
MPO
(5/23) in patients with a diagnosis of
Wegener's granulomatosis
. By contrast, anti-
MPO
was found in a majority of vasculitis patients without extrarenal symptoms (6/9), including 3 patients treated with hydralazine. One of the patients treated with hydralazine had circulating ANCA in combination with anti-
MPO
. Anti-
MPO
was also found in 1 out of 6 patients with Goodpasture's syndrome. The findings emphasize that autoantibodies to distinct components of neutrophil granulocytes partly differ with regard to diagnostic specificity.
...
PMID:Antimyeloperoxidase antibodies in patients with extracapillary glomerulonephritis. 217 10
Circulating antibodies directed against cytoplasmic constituents of granulocytes and monocytes (anti-neutrophil cytoplasm antibodies, ANCA) are found in about 80% of active cases of
Wegener's granulomatosis
and microscopic polyarteritis. Antibodies are detected by indirect immunofluorescence on normal peripheral blood leucocytes, or by ELISA or radio-immunoassay using a neutrophil cytoplasm extract. There are 2 patterns of staining seen on indirect immunofluorescent examination of leucocytes and a number of different molecules recognised on Western blots. In
Wegener's granulomatosis
diffusely granular cytoplasmic staining (cANCA) is associated with a 29KD molecule that has recently been identified as neutrophil proteinase 3. A finely granular pattern may also be seen in microscopic polyarteritis. A perinuclear pattern (pANCA) is present in some other cases of segmental necrotising glomerulonephritis and occasionally in rheumatoid arthritis but almost never in
Wegener's granulomatosis
. This pattern is often associated with the presence of anti-
myeloperoxidase
and anti-elastase antibodies. Levels of anti-neutrophil cytoplasm antibodies usually reflect disease activity but a pathogenetic role for these antibodies in the development of small vessel vasculitides is, as yet, unproven.
...
PMID:Anti-neutrophil cytoplasm antibodies (ANCA). 219 72
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