Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-neutrophil antibodies have been shown in sera from patients with a variety of inflammatory diseases. Those reacting with components of neutrophil cytoplasm are associated with systemic vasculitis. Both nuclear and perinuclear staining patterns on human neutrophils have been reported using sera from patients with inflammatory bowel disease. We have evaluated the reactivity against human neutrophils of sera from 100 patients with inflammatory bowel disease, 14 disease controls, and 20 normal volunteers. Altogether 27/50 (54%) sera from patients with ulcerative colitis contained antibodies that reacted with cytospun ethanol fixed neutrophils compared with 5/50 (10%) from Crohn's disease (p less than 0.001) and 0/34 control sera (p less than 0.001). All seven sera from patients with proctitis alone were negative (p less than 0.01). There was no correlation between presence or titre of anti-neutrophil antibodies and either disease activity or treatment. Positive sera gave three different staining patterns on human neutrophils. The predominant pattern was perinuclear (17/32); 12 sera gave a cytoplasmic and three a homogeneous nuclear staining pattern. None of the patients or the controls had antibodies to myeloperoxidase, elastase, or serine proteinase 3, all of which are recognised by anti-neutrophil cytoplasmic antibodies. Only 2/27 sera positive by indirect immunofluorescence reacted with an extract of neutrophil primary granules. In conclusion, anti-neutrophil antibodies occur more commonly in ulcerative colitis than in Crohn's disease or control subjects and the anti-neutrophil antibodies found in inflammatory bowel disease are different from those associated with vasculitis.
 ...
PMID:Anti-neutrophil antibodies in inflammatory bowel disease: prevalence and diagnostic role. 161 85

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.
 ...
PMID:How are antineutrophil cytoplasmic autoantibodies detected? 186 72

Rocky Mountain spotted fever (RMSF) takes its name from the characteristic rash that occurs as a consequence of vasculitis associated with rickettsial invasion of the endothelium. The authors examined sera from 14 patients with serologically confirmed RMSF for the presence of antibodies (IgG and IgM) reactive with human umbilical vein-derived endothelial cells and with the phospholipids cardiolipin (CL) and phosphatidyl serine (PS). Sera from 7 patients (50%) exhibited antiendothelial antibodies, and 10 (71%) patient sera reacted with CL and/or PS. Because such antibodies may interfere with or augment endothelial thrombosis-related activities, acute and convalescent sera were tested for their effects on endothelial PGI2 secretion and protein C activation. Acute sera from two patients and convalescent sera from four patients stimulated protein C activation. Additionally, sera from five acute and nine convalescent cases inhibited basal endothelial PGI2 secretion, but sera from two acute and three convalescent cases stimulated thrombin-dependent PGI2 secretion. These results demonstrated that, in a significant proportion of patients, RMSF was accompanied by the appearance of antibodies that bound to endothelial cells and to phospholipids; some of these antibodies may have altered anticoagulant endothelial functions.
 ...
PMID:Serologic characterization of Rocky Mountain spotted fever. Appearance of antibodies reactive with endothelial cells and phospholipids, and factors that alter protein C activation and prostacyclin secretion. 202 28

In this article new informations about systemic vasculitis were reviewed. Evaluation of ANCA and their antigen specificity is of a great help in classification of systemic vasculitis. Among idiopathic systemic vasculitis anti-serine proteinase antibodies are found in Wegener granuloma, anti-MPO antibodies in Churg-Strauss syndrome and in polyarteritis nodosa. Antibodies against other components of PMNL granules still remain unknown. The main purpose of this review was to underline incidence of systemic vasculitis and the meaning of ANCA in the diagnosis and classification of these diseases.
 ...
PMID:[Autoantibodies against neutrophil cytoplasm and their significance in the classification of systemic vasculitis]. 756 88

A 42-year-old housewife was admitted to our hospital because of an asthma attack, fever, severe eosinophilia, mononeuritis-multiplex, arthralgia, skin-eruptions, transient pulmonary infiltration, and other symptoms. Chung-Strauss syndrome was diagnosed. When there were signs and symptoms of vasculitis, chest radiography revealed that pulmonary infiltrates had decreased, but her chest CT showed ground glass opacities of both lung fields and fine granular shadows. Differential cell count of bronchoalveolar lavage fluid revealed a high level of eosinophils, and transbronchial lung biopsy specimens showed vasculitis and marked infiltration of eosinophils. When signs and symptoms of vasculitis were prominent, antineutrophil cytoplasmic antibodies (ANCA) in the serum were examined. PR3-ANCA (antibodies to serine-protease, nearly equal to c-ANCA), which is specific to Wegener's granulomatosis, was negative, but MPO-ANCA (antibodies to myeloperoxidase, nearly equal to p-ANCA) was positive and the level was very high (478 EU/ml). After corticosteroid therapy, her symptoms markedly improved, and MPO-ANCA became negative. MPO-ANCA appeared to reflect the disease activity in this case.
 ...
PMID:[A case of Churg-Strauss syndrome in which MPO-ANCA (antibodies to myeloperoxidase) appeared to reflect the disease activity]. 760 41

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)
 ...
PMID:Inhibition of proteinase 3 by ANCA and its correlation with disease activity in Wegener's granulomatosis. 764 21

Although precise diagnosis of the systemic vasculitides can provide general prognostic information and help to guide initial therapy, recent studies on the long-term clinical course have revealed considerable variation in clinical severity. Therefore, anatomic distribution of involvement and speed of progression should be the principle determinants of the intensity of immunosuppressive therapy. In progressive pulmonary or renal disease, eg, Wegener's granulomatosis, aggressive "standard" therapy is obligatory, eg, daily cyclophosphamide and glucocorticoids. Such regimens, however, should be applied with caution in chronic or indolent and abortive forms of systemic vasculitis, because follow-up studies (eg, in Wegener's granulomatosis) have revealed treatment-associated morbidity rates of up to 42%, disease-related morbidity, and a high incidence of relapse under treatment. Moreover, less toxic therapeutic strategies are being pursued with remarkable success: low-dose weekly methotrexate, monthly intravenous or oral pulses of cyclophosphamide plus glucocorticoids, and high-dose intravenous immunoglobulin. Long-term remission of intractable (non-antineutrophil cytoplasmic antibody-associated) systemic vasculitis has been achieved using humanized monoclonal antibodies (ie, anti-CD4/anti-CDw52); and amelioration of glomerulonephritis in immune complex diseases (eg, systemic lupus erythematosus) has been achieved with nafamostat mesilate, an inhibitor of complement serine proteases. In addition, leukocytoclastic vasculitis has been effectively controlled with pentoxifylline, presumably by neutralizing proinflammatory cytokines, and hepatitis C virus-associated mixed cryoglobulinemia has been successfully treated with interferon alfa.
 ...
PMID:New developments in the treatment of systemic vasculitis. 803 74

Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with clinically proven vasculitis have been described as reacting with proteins present in the granules of human neutrophils. We have studied sera from 59 ANCA positive patients to further characterize the antibody response. In addition to the antigens previously identified in the vasculitic syndromes (myeloperoxidase and serine proteinase 3) the majority of these sera contained antibodies that reacted with a cytosolic extract of neutrophils on Western blots. Nearly 40% of these sera had antibodies directed against a cytosolic protein(s) of molecular mass 48 kD. This protein was purified from neutrophil cytosol by ammonium sulphate fractionation, anion exchange and reverse phase chromatography. Amino acid sequence analysis of a proteolytic fragment of this protein identified it as alpha enolase. The anti-enolase antibodies only recognized the alpha isoform and were present in sera giving either a pANCA or cANCA staining pattern by indirect immunofluorescence. Antibodies to alpha enolase were also found in sera from patients with systemic lupus erythematosus, particularly those with renal disease. We conclude that the antibody response in ANCA positive vasculitis is not restricted to neutrophil granule proteins.
 ...
PMID:Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. 845 67

We isolated a 27-kD protein using cation exchange chromatography from an acid extract of neutrophil granules. N-terminal amino acid sequence analysis of the first 10 residues showed that this protein is azurocidin, a member of the family of neutral serine proteinase found in the neutrophil, which shares amino acid sequence homology with the three other neutral serine proteinases, elastase, proteinase 3 (PR3) and cathepsin G, but unlike them is without proteolytic activity. To test whether, in addition to these proteases, azurocidin might be a target for the humoral autoimmune responses associated with human vasculitis, 185 indirect immunofluorescence (IIF)-positive ANCA sera, made up of four groups of sera with specificities for PR3 (n=37), myeloperoxidase (MPO; n=50), bactericidal/permeability-increasing protein (BPI; n=41) and sera that recognized none of them (triple negative, n=57), and 46 normal sera were screened for IgG anti-azurocidin antibodies using an ELISA incorporating purified azurocidin. Twenty of the 185 IIF-positive sera and 2/46 normal sera displayed reactivity with azurocidin. Positive sera could blot the 27-kD band by Western blot analysis. Further study of the 20 positive sera revealed that: (i) 10 also had autoreactivity for MPO, of which six additionally recognized lactoferrin; (ii) two had reactivity with BPI; (iii) the remaining eight sera were positive only for azurocidin. All 20 sera were from patients with systemic vasculitis, and four of the six sera with triple reactivity (for azurocidin, MPO and lactoferrin) were from patients with hydralazine-induced vasculitis. We concluded that: (i) azurocidin is a novel ANCA antigen; (ii) anti-azurocidin antibodies from a subgroup of patients might represent the consequence of a drug-induced multi-clone activation.
 ...
PMID:Azurocidin is a novel antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in systemic vasculitis. 860 37

Cytoplasmic antineutrophil cytoplasmic antibodies (cANCA) that accompany the neutrophilic vasculitis seen in Wegener's granulomatosis (WG), are directed against proteinase-3 (PR-3), a serine proteinase which is located in azurophilic granules of neutrophils and monocytes. PR-3, when expressed on the surface of TNFalpha-primed neutrophils, can directly activate neutrophils by complexing cANCA and promoting concomitant Fcgamma receptor (FcgammaR) cross-linking. Although the neutrophil's pathogenic role in WG has been studied, the role of the monocyte has not been explored. The monocyte, with its ability to release cytokines and regulate neutrophil influx, also expresses PR-3. Therefore, the monocyte may play a significant role in WG via the interaction of surface PR-3 with cANCA, inducing cytokine release by the monocyte. To test this hypothesis, monocytes were studied for PR-3 expression and for IL-8 release in response to cANCA IgG. PBMC obtained from healthy donors displayed dramatic surface PR-3 expression as detected by immunohistochemistry and flow cytometry in response to 0. 5-h pulse with TNFalpha (2 ng/ml). Purified monoclonal anti-PR-3 IgG added to TNFalpha-primed PBMC induced 45-fold more IL-8 release than an isotype control antibody. Furthermore, alpha 1-antitrypsin (alpha1-AT), the primary PR-3 antiprotease, inhibited the anti-PR-3 induced IL-8 release by 80%. Importantly, Fab and F(ab')2 fragments of anti-PR-3 IgG, which do not result in Fcgamma receptor cross-linking, do not induce IL-8 release. As a correlate, IgG isolated from cANCA positive patients with WG induced six times as much PBMC IL-8 release as compared to IgG isolated from normal healthy volunteers. Consistent with PR-3 associated IL-8 induction, alpha1-AT significantly inhibited this effect. These observations suggest that cANCA may recruit and target neutrophils through promoting monocyte IL-8 release. This induction is mediated via Fcgamma receptor cross-linking and is regulated in part by alpha1-AT.
 ...
PMID:Antineutrophil cytoplasmic antibodies induce monocyte IL-8 release. Role of surface proteinase-3, alpha1-antitrypsin, and Fcgamma receptors. 929 7


1 2 3 4 Next >>