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)

The antigenic specificity and clinical distribution of the antineutrophil cytoplasmic antibodies (ANCA) in kidney diseases have recently been extensively studied. In patients with systemic vasculitis, the great predominance of two major ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO), is now established. PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation, and thus are able to interact with autoantibodies after neutrophil preactivation. Furthermore, by comparison of amino acid and DNA sequences, it has been shown that PR3 is identical to myeloblastin, which has been described independently and is involved in the control of growth and differentiation of leukemic cells. Aside from the two major ANCA antigens, a number of neutrophil cytoplasmic antigens recognized by ANCA have been identified, including human leukocyte elastase, lactoferrin, CAP57, and cathepsin G. These rare ANCA specificities occur in a limited number of patients. The variety of ANCA antigen specificities contrasts, however, with the fact that the vast majority of ANCA-positive sera are monospecific for one single ANCA antigen. With regard to clinical distribution, ANCA have major diagnostic significance in the four conditions in which they are frequently detected: Wegener's granulomatosis (WG), Churg and Strauss Syndrome (CSS), microscopic periarteritis (MPA), and necrotic and crescentic glomerulonephritis (NCGN). However, the initial dichotomy between MPO-associated vasculitis (NCGN, MPA) and that associated with anti-PR3 antibodies (WG) appears far from absolute.
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PMID:Antigen specificities and clinical distribution of ANCA in kidney diseases. 172 65

Immunohistochemical studies were performed on the temporal artery of 34 patients with clinically established polymyalgia rheumatica (PR) or temporal arteritis, 6 patients with vasculitis, and 25 patients with various diseases. The combined immunofluorescence and peroxidase-anti-Peroxidase Methode zeigte Immunoglobulin- und C3-Ablagerunin histologically affected and to some degree also in unaffected arteries of patients with PR and in all patients with temporal arteritis. The deposits were found both inter- and intracellularly, and contained IgA and to a lesser extend IgG, IgM, and C3. Linear deposits of leukocyte elastase were found along the fragmented internal lamina, and decaying polymorphonuclear (PMN) leukocytes surrounded by elastase-containing inclusions were found in the neighborhood of zones rich in elastic material. These findings suggest that immune complex deposition is a prominent feature of temporal arteritis and that the PMN elastase is probably involved in the destruction of elastic fibers. The combined immunohistochemical investigation appears to increase the diagnostic value of temporal artery biopsy.
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PMID:Temporal arteritis in polymyalgia rheumatica: immune complex deposits and the role of the leukocyte elastase in the pathogenesis. 655 32

We studied the presence of proteinase 3 (PR3), myeloperoxidase (MPO) and elastase (HLE) on the plasma membrane of neutrophils in patients with biopsy-proven Wegener's disease (WG), pANCA-positive vasculitis, control patients (SLE, rheumatoid arthritis, ankylosing spondylitis), sepsis patients and healthy donors. We found an overexpression of PR3 on the cell surface of neutrophils in WG, ANCA-associated vasculitis and during infection (sepsis). Thus PR3 becomes accessible to ANCA. Furthermore we detected intracytoplasmic IgG antibodies in PMN from patients with WG by immunoelectron microscopy and direct immunofluorescence. Our findings support the pathophysiological role of ANCA.
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PMID:Membrane surface proteinase 3 expression and intracytoplasmic immunoglobulin on neutrophils from patients with ANCA-associated vasculitides. 829 55

A 39-year-old Japanese woman had been receiving propylthiouracil for 5 years for hyperthyroidism when she developed myalgia, scleritis, proteinuria, fever, and inflammation of the nose. Examination of a renal biopsy specimen showed focal segmental necrotizing glomerulonephritis. Indirect immunofluorescent staining showed a highly positive perinuclear pattern of anti-neutrophil cytoplasmic antibody (ANCA) in her serum. Enzyme-linked immunosorbent assay (ELISA) of the ANCA showed positivity for anti-proteinase 3, anti-myeloperoxidase, anti-leukocyte elastase, and anti-lactoferrin, but anti-cathepsin G and anti-lysozyme were negative. Because ELISA showed the titer of anti-leukocyte elastase antibody to be markedly elevated, we challenged this data by performing dot blot analysis. The patient's serum reacted with the native form, but not with denatured leukocyte elastase. Propylthiouracil-induced vasculitis was suspected. Symptoms abated within 2 weeks and all values of ANCA were reduced after the drug was withdrawn. Vasculitis is a rare side-effect of propylthiouracil therapy. Recently it was reported in association with ANCA. We present the findings of this patient and compare them with those described in 19 published cases of propylthiouracil-induced vasculitis associated with ANCA.
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PMID:Case of propylthiouracil-induced vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA); review of literature. 918 Dec 82

This prospective study was designed to determine the role of antineutrophil cytoplasmic autoantibodies (ANCA) in HIV-infected patients. Immunofluorescence tests (IFT) and enzyme-linked immunosorbent assays (ELISA) were applied to sera of 199 consecutive outpatients. In the IFT 20% were positive. An atypical ANCA pattern was demonstrated in 67% of these, 33% revealed a perinuclear staining (pANCA). Specific ELISA revealed proteinase 3 (n = 2), myeloperoxidase (n = 1), lysozyme (n = 2), lactoferrin (n = 1), cathepsin G (n = 1), and human leukocyte elastase (HLE, n = 6). The target antigen remained unidentified in 26 patients. Perinuclear ANCA-positive patients showed atypical antigens in eight of 13 cases; all six patients with anti-HLE revealed a pANCA pattern. The antigens of atypical ANCA-positive patients remained unidentified in 21 of 26 (81%) cases. No signs of vasculitis were present in the ANCA-positive patients. ANCA are frequently found in the sera of HIV-positive patients. They bind to a variety of antigens. No correlation was found between ANCA positivity and autoimmune or opportunistic diseases.
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PMID:Seroprevalence and disease association of antineutrophil cytoplasmic autoantibodies and antigens in HIV infection. 1021 37

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies against enzymes present in primary granules of neutrophils and lysosomes of monocytes detected in systemic vasculitis and in other diseases, including infections. ANCA are markers of active Wegener granulomatosis, which presents some anatomo-pathologic and immune response features similar to those of leprosy. Thus, we raised the hypothesis that ANCA may be present in leprosy as markers specifically linked to the presence of vasculitis. The aim of this study was to determine the presence of ANCA in leprosy and its correlation with the clinical forms of the disease. Sera from 60 normal individuals and from 59 patients with different clinical forms of leprosy were studied. The patients were also allocated into reactional and nonreactional groups. By indirect immunofluorescence, ANCA were positive, an atypical pattern (A-ANCA), in 28.8% of the patient sera. A-ANCA predominated, although not significantly (p > 0.05), in the reactional groups 37.9% vs 20.0%), and in those at the lepromatous pole (41.6% vs 20.0%). There was no correlation between ANCA positivity and either disease duration, disease activity, or therapeutic regimen (p > 0.05). An interesting finding was the correlation between ANCA and gender: 94.1% of ANCA-positive patients were males (p < 0.01), a feature that so far has not been reported in ANCA-related diseases and for which there is no explanation at the moment. By ELISA, the sera of the lepromatous leprosy patients did not show activity against either PR3, MPO, HLE, the most common ANCA antigens. Because A-ANCA are nonspecific, this finding requires further investigation for the determination of the responsible antigen(s). In conclusion, A-ANCA are present in 28.8% of leprosy patients but are not related to vasculitis in the erythema nodosum leprosum reaction and are not a marker of a specific clinical form.
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PMID:Anti-neutrophil cytoplasmic antibodies (ANCA) in the clinical forms of leprosy. 1034 68

We examined whether the lung injury produced in rats by intraperitoneal injection of the superantigen, staphylococcal enterotoxin B (SEB), could be inhibited by intravenous preadministration of human urinary trypsin inhibitor (UTI), which exhibits multipotent inhibitory effects on serine proteinases such as plasmin, chymotrypsin, or human leukocyte elastase or cathepsin G, since preliminary experiments showed the ability of UTI to bind lipopolysaccharides and bacterial toxins. For ligand blotting analysis, four kinds of toxins were run on a slab gel and the binding of UTI to the toxins was visualized by immunoblotting. Lung tissue from 26 rats was used for immunohistochemistry using a mouse antirat CD 45 mAb and an antirat macrophage mAb. Lung tissue from 31 rats was used for measurement of myeloperoxidase activity before and after intraperitoneal injection of SEB, after infusion of PBS, UTI, PBS-SEB or UTI-SEB combination. Ten of the 26 rats described above were used for electron microscopy. Rat sera were used for measurement of TNF-alpha. Statistical analysis was performed using the Mann-Whitney U-test. Intraperitoneal injection of SEB caused an increase in the number of punctate areas of haemorrhage on the surface of the lung with time, and histological examination revealed lung injuries with different extents, vasculitis where inflammatory cells were concentrated, and infiltration of numbers of eosinophils into the alveolar septa. However, preadministration of UTI for rats markedly attenuated lung injury and vasculitis induced by intraperitoneal injection of SEB. This revealed, from a marked reduction in the number of inflammatory cells and the extent of injury, a marked inhibition of serum TNF-alpha production and reduction of myeloperoxidase content of rat lungs compared to controls. UTI may have defensive effects to infection by suppressing the early responses of stimulated cells to activated stimulus such as SEB as well as the release of stimulant-mediated cytokines via trapping of bacterial toxins.
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PMID:Suppression of superantigen-induced lung injury and vasculitis by preadministration of human urinary trypsin inhibitor. 1126 57

Antineutrophil cytoplasmic antibodies (ANCA) are present in sera from patients with various forms of vasculitis-associated glomerulonephritis. Because autoantibodies may be directed against antigens presented by apoptotic cells, generation of ANCA using apoptotic neutrophils (PMN) in syngenic Brown Norway (BN) rats was attempted. These rats are T-helper type 2-prone animals, already used successfully in other ANCA-positive animal models. BN rats received repeated injections of buffer or of nonapoptotic or apoptotic PMN aged in cultures, in the footpad and once intravenously. Four of five rats that received injections of PMN aged for 48 h developed ANCA, which cross-reacted with human leukocyte elastase in three cases. None of the rats that received injections of freshly isolated neutrophils developed ANCA. One rat that received buffer injection and that exhibited chronic skin infection developed delayed ANCA. None of the rats showed signs of disease: no weight loss and no proteinuria. Then a subnephritogenic dose of antibody directed against rat glomerular basement membrane was injected. Rats then were killed, and different organs were frozen and studied. No significant lesions were found in kidneys or lungs. It is concluded that injections of apoptotic but not freshly isolated PMN can generate ANCA in BN rats. Additional studies are needed to elucidate the immunization mechanism and the ability of these autoantibodies to initiate vasculitis in these experimental animals.
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PMID:Rats injected with syngenic rat apoptotic neutrophils develop antineutrophil cytoplasmic antibodies. 1146 51

The detection rate of antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with clinically suspected small vessel vasculitis was investigated, and their antigen specificity and demographic features were analyzed. A number of sera (n = 5,604) sent to our referral laboratory for ANCA screening were tested by indirect immunofluorescence (IIF), enzyme-linked immunosorbent assays (ELISAs) for myeloperoxidase (MPO)- and proteinase 3 (PR3)-ANCA. Then the IIF-ANCA-positive sera that were negative for MPO- and PR3-ANCA were further tested by antigen-specific ELISA by using other five highly purified known ANCA antigens as solid-phase ligands. The known antigens included bactericidal/permeability-increasing protein (BPI), human leukocyte elastase (HLE), lactoferrin, cathepsin G, and azurocidins. Of the 5,604 sera, 267 (4.76%) sera were IIF-ANCA positive and 390 (7%) were antinuclear antibody (ANA) positive in the IIF assay. Of the IIF-positive samples, 213 were anti-MPO positive, 32 were anti-PR3 positive, and five cases were positive for both. Of the 48 sera positive for IIF-ANCA but negative for MPO- and PR3-ANCA, 13 sera (27%) recognized other target antigens, 7 sera recognized BPI, 5 recognized HLE, 1 recognize cathepsin G, and 1 recognized azurocidin. None of the sera recognized lactoferrin, and one serum sample recognized both BPI and HLE. The majority of ANCA-positive patients presented in summer or winter. There was no difference in gender (male/female ratio, 1:1.12) in ANCA-positive patients with a mean age of 53.1 years. The male/female ratio was 1.17:1 for patients over 60 years of age; however, it was 1:4 for patients under 20 years of age. We conclude that ANCA-related diseases are not rare in China, and the major antigens are MPO and PR3. When the IIF technique is used to detect ANCA, ANA should be carefully distinguished.
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PMID:Detection rate and antigenic specificities of antineutrophil cytoplasmic antibodies in chinese patients with clinically suspected vasculitis. 1513 82

Alpha-1 antitrypsin (AAT) deficiency is a common but under-recognized disease. This hereditary disorder is characterized by low levels of AAT, and increased risks of panacinar emphysema at an early age, liver disease, vasculitis and panniculitis. Destruction of lung parenchyma and consequent emphysema result from an imbalance between different inflammatory proteases (in particular, leukocyte elastase), and the major natural antiprotease, AAT. To offer a review of key aspects of this important condition, we present the epidemiology, natural history, and pathogenesis of AAT deficiency and, in the context of recent data and the publication of an international standards document regarding the diagnosis and management of individuals with AAT deficiency, review current therapy of AAT deficiency.
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PMID:A review of alpha-1 antitrypsin deficiency. 1713 53


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