Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is accumulating evidence that anti-phospholipid (aPL) antibodies in the sera of patients with autoimmune diseases bind to a complex of anionic phospholipids and plasma phospholipid-binding proteins, namely beta 2-glycoprotein I (beta 2-GPI) and prothrombin. It has been suggested that a conformational change in beta 2-GPI, induced by binding either to anionic phospholipids or to the oxygen molecules on the irradiated microtiter plate, reveals cryptic antigenic epitope(s) in the native protein. We used an enzyme-linked immunoassay for measuring antibodies against two phospholipid-binding proteins, i.e., beta 2-GPI and prothrombin, absorbed to an irradiated plate in an unselected series of 139 patients with systemic lupus erythematosus (SLE). Elevated levels of antibodies against beta 2-GPI were found in 49% of patients and antibodies against prothrombin in 34% of patients. Both antibodies were significantly associated with deep venous thrombosis in patients with SLE (P = 0.009 for both antibodies). Accordingly, testing of these antibodies seems to be clinically useful in evaluating the risk of thrombosis.
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PMID:Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus. 867 35

During late seventies it became apparent that the appearance of antiphospholipid antibodies is associated with thromboembolic manifestations, such as cerebral or myocardial infarction, pulmonary thromboembolism, deep vein thrombosis, intrauterine fetal losses and thrombocytopenia. The term antiphospholipid syndrome has been used to define this set of pathologic features. Recognition of this syndrome has spread worldwide as its clinical implications have become appreciated. Recent studies showed that cofactor, beta 2-glycoprotein I (beta 2-GPI) is required for binding of anticardiolipin antibodies (aCL) raised in the patients with SLE and related other autoimmune disorders. However, this finding has generated considerable controversy. Four different hypotheses have been proposed to explain the specificity of aCL: (1) CL is directly recognized by aCL; (2) the beta 2-GPI-CL complex is the structure recognized by aCL; (3) the beta 2-GPI is the actual target antigen for aCL but is cryptic in the absence of CL; and (4) the actual epitope for aCL appears on the native structure of beta 2-GPI. We showed that aCL bound to beta 2-GPI interacting with poly-oxygenated plates and in the absence of CL, an interaction which depends on introduction of oxygen atoms on the polystyrene surface. We also showed that the beta 2-GPI bound to CL via a particular region on the fifth domain, namely C281KNKEKKC288, and the tertiary structure of the region is involved in binding to phospholipid. Several mechanisms to explain the vascular injury and thrombosis associated with aCL have been proposed, primarily based on their phospholipid reactivity to activated platelets. Whether aCL-through binding to complex of beta 2-GPI and negatively charged phospholipid in the phospholipid-dependent coagulation reactions of hemostasis contribute to the increased risk of thrombosis in patients with aCL is an important question in need of an answer. We have demonstrated the possibility that not only activated platelets but also oxidized lipoproteins, e.g., low-density lipoprotein (LDL), may be thrombogenic targets of aCL which recognize the altered beta 2-GPI structure.
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PMID:[Autoantibodies and thrombosis]. 936 65