Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wegener's granulomatosis (WG) is a granulomatous necrotizing vasculitis associated with the presence of ANCA, predominantly directed against proteinase 3 (PR3). The titres of ANCA correlate with disease activity and titre increases may precede disease exacerbations. Previously, we have shown that it is possible to induce autoimmune disease (systemic lupus erythematosus (SLE) and anti-phospholipid syndrome) in naive mice following active immunization with human autoantibodies, namely anti-DNA and anti-cardiolipin, respectively. The mice developed first anti-autoantibodies and, after about 4 months anti-anti-autoantibodies (Ab3), simulating auto-antibodies (Ab1) in their binding activities, and their presence was associated with the development of disease manifestations, characteristic of the human disease. So far, there is no good animal model for WG. In the current study we have immunized mice with human ANCA with the aim of inducing experimental WG. In two separate studies 30 mice were immunized in their footpads with autoantigen-purified IgG fraction (ANCA) from the sera of two patients with untreated WG, emulsified in Freund's complete adjuvant, followed 3 weeks later by ANCA injection in PBS. In the first experiment mice immunized with ANCA developed sterile microabscesses in the lungs after 8 months, and died after 8-15 months. In the second experiment, mice immunized with ANCA developed after 4 months mouse ANCA, with specificity both to PR3 and to myeloperoxidase, as well as anti-endothelial autoantibodies (AECA), as shown by radioimmunoprecipitation. Pathologically, the immunized mice developed proteinuria but not haematuria, and histological sections of the lungs demonstrated mononuclear perivascular infiltration, while diffuse granular deposition of immunoglobulins was noted in the kidneys. Our results point to a pathogenic role of ANCA in WG, and confirm the importance of the idiotypic network in the etiopathogenesis of autoimmune conditions.
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PMID:Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration. 755 78

Systemic autoimmune diseases, such as vasculitis and collagen diseases, are characterized by chronic inflammation. Mutual interrelationship between angiogenesis and chronic inflammation has already been demonstrated. The aim of the study was to examine the effect of sera from patients with systemic autoimmune diseases on angiogenesis induced by human mononuclear cells. The study population consisted of 43 patients with a systemic autoimmune disease associated with pulmonary manifestations, divided into three groups: 14 with Wegener's granulomatosis (WG), 13 with systemic sclerosis (SS), and 16 with collagen vascular diseases (CVD) such as rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis. The control group consisted of 15 healthy volunteers. Clinical status was evaluated using a questionnaire. Standard chest radiographs were performed in all patients. Pulmonary function tests were performed according to the ERS standards. An animal model of a leukocyte-induced angiogenesis assay was used as an angiogenic test. Sera from WG and CVD patients significantly stimulated angiogenesis compared with healthy subjects (P<0.001). On the other hand, sera from healthy donors exerted a proangiogenic effect compared with PBS. In contrast, sera from SS patients significantly (P<0.001) inhibited angiogenesis compared with sera from healthy subjects and PBS. Proangiogenic effect of sera from systemic diseases patients depended on radiological changes. No significant correlation between a degree of dyspnea or functional pulmonary tests and the number of new vessels or angiogenesis index was found. Sera from patients with systemic autoimmune diseases and healthy people constitute the source of mediators modulating angiogenesis. These modulatory effects differ depending on the disease entity.
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PMID:Angiogenic activity of sera from patients with systemic autoimmune diseases in relation to clinical, radiological, and functional pulmonary status. 1921 6