Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoantibodies to prothrombin are common in patients with systemic lupus erythematosus. Although their presence is a risk factor for thrombosis, neither their origin nor their precise role in inducing the procoagulant state is known. We have developed a phage-display antibody library from patients with systemic lupus erythematosus with antiprothrombin antibodies, and we have selected two single-chain Fv antibody fragments (ScFvs) by panning on a prothrombin-coated surface. In prothrombin activation assays using purified components, these antibodies promoted prothrombin activation. These ScFvs, termed AN78 and AN129, bound to immobilized prothrombin in a concentration-dependent specific manner but not to other anionic phospholipid binding proteins such as beta2-glycoprotein I or annexin V. Phosphatidylserine-bound prothrombin, but not soluble prothrombin, inhibited the binding suggesting that the epitope is available only on immobilized prothrombin. To localize the epitope, prothrombin was treated with thrombin or factor Xa and various prothrombin activation fragments were subsequently isolated and tested in ELISA with the ScFvs. Both AN78 and AN129 bound to prethrombin I (the fragment lacking the Gla domain and the first kringle domain), to fragment 1.2 (containing Gla and the two kringle domains only) and to fragment 2 but not to thrombin, thus localizing the cognate epitope to the kringle 2 domain in prothrombin. Analysis of the cDNA sequences of these antibodies show clustered mutational patterns in the complementarity determining region, suggesting that variable domains are the products of antigen-driven B cell clonal maturation.
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PMID:Lupus-derived antiprothrombin autoantibodies from a V gene phage display library are specific for the kringle 2 domain of prothrombin. 1504 12

Antiphospholipid antibodies detected by lupus anticoagulant, anticardiolipin or anti-beta2 glycoprotein I assays were associated with fetal loss. Rather than being diagnostic tools only, antiphospholipid antibodies are thought to be pathogenic. The strongest demonstration of their pathogenic role lies in the ability to induce fetal resorptions--the experimental equivalents of the human fetal losses--when passively infused in pregnant naive animals. However, still debated is how the antibodies might induce the obstetrical manifestations. Thrombotic events at the placental levels might be related to endothelial cell activation, inhibition of protein C/S system and fibrinolysis as well as to Annexin V displacement. However, the thrombophilic state apparently cannot explain all the miscarriages and a direct antibody-mediated damage on the trophoblast has been suggested. During differentiation to syncytium, trophoblasts express cell membrane anionic phospholipids that can bind beta2 glycoprotein I, the main cationic phospholipid binding protein recognized by the antiphospholipid antibodies. Adhered beta2-glycoprotein I might be recognized by the antibodies that, once bound, strongly interfere with in vitro trophoblast cell maturation so resulting in a defective placentation. These mechanisms have been suggested to play a role in early fetal loss, while thrombotic events would be responsible for miscarriages late in the pregnancy.
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PMID:Antiphospholipid antibodies as cause of pregnancy loss. 1548 95

Whereas antiphospholipid antibodies (aPL) are associated with thrombotic events and recurrent spontaneous abortion (RSA), the contribution of anti-beta2 glycoprotein 1 (beta2GP1) and anti-annexin V antibodies as risk factors for RSA remain poorly understood. We investigated anti-beta2-GPI and anti-annexin V IgM and IgG antibodies as potential risk factors for RSA in 200 women with more than three consecutive idiopathic RSA, and 200 age-matched, healthy, parous women. Pearson's chi squared test analysis showed that while anti-beta2-GPI IgG (P = 0.416) and IgM (P = 0.72) were comparable between patients and controls, elevated anti-annexin V IgG (P = 0.006), but not IgM (P = 0.084), was more pronounced in patients. Higher frequencies of elevated IgG-only (P = 0.005), but not IgM-only (P = 1.000; OR = 6.66), anti-annexin V antibodies were noted among patients. Multinomial regression analysis showed that body-mass index (overweight and obesity; P = 0.008), education status (P < 0.001) and anti-beta2-GPI IgM (P = 0.033), but not IgG (P = 0.723), were associated with early abortion, while anti-beta2-GPI IgG (P = 0.030) and anti-annexin V IgG (P = 0.004) were associated with late RSA. For combined early-late RSA, the only variable selected was education status (P < 0.001), and neither anti-annexin V nor anti-beta2-GPI IgM and IgG was associated with early-late RSA. Accordingly, anti-annexin V and anti-beta2-GPI should be regarded as independent risk markers of RSA.
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PMID:A case-control study on the association of idiopathic recurrent pregnancy loss with autoantibodies against beta2-glycoprotein I and annexin V. 1659 32

Anti-phospholipid syndrome (APS) is defined based on both clinical findings (recurrent arterial and/or venous thrombosis and recurrent fetal loss) and laboratory evidence of persistent anti-phospholipid antibodies (anti-cardiolipin antibodies, anti-beta2 glycoprotein I antibodies, or LA activity). However, the precise mechanism responsible for arterial and/or venous thromboembolic complications in APS patients remains unclear. To clarify the association between the various types of anti phospholipid antibodies (aPLs) and thrombotic complications, we examined the prevalence of seven types of aPLs [anti-cardiolipin/beta2-glycoprotein I antibodies(anti-CL/beta2-GPI), anti-phosphatidylserine/prothrombin antibodies(anti-PS/PT), anti-beta2-glycoprotein I antibodies (anti-beta2-GPI), anti prothrombin antibodies (anti-PT), anti-protein C antibodies (anti-PC), anti-protein S antibodies(anti-PS), and annexin V antibodies(anti-AN)] in 168 patients with systemic lupus erythematosus (SLE). We confirmed that the presence of anti-CL/beta2-GPI, anti-PS/PT, and anti-beta2-GPI is closely related to arterial thrombosis, and that the presence of anti-protein S is closely related to venous thromboembolism. Furthermore, our in-vitro experiment suggests that anti-CL/beta2-GPI and anti-PS/PT may cooperate to promote platelet activation, and may be involved in the pathogenesis of arterial thrombosis. On the other hand, anti-protein S led to APC resistance, which may represent an important mechanism responsible for the development of venous thrombosis. Furthermore, our study showed that anti-CL/beta2-GPI causes a persistently high-level expression of tissue factor on monocytes, and this may increase the risk of atherosclerosis.
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PMID:[Advanced clinical laboratory studies in the graduate school of medicine--studies on pathogenic mechanisms of anti-phospholipid syndrome]. 1976 14

We investigated the serum levels of IgG and IgM anticardiolipin (ACL), anti-beta-2-glycoprotein I (B2GPI), anti-phosphatidyl serine (PS), anti-prothrombin(PT), anti-annexin V (AnV) and anti-ethanolamine (Eth) antibodies using an ELISA method (Orgentec, Germany) in 16 females with normal pregnancy in the I, II and Ill trimester. We observed the following changes: 1. Elevation of the IgG u IgMACL, IgG PS, IgM Pr antibodies in the II and decreasing in the Ill trimester. 2. Decreasing of IgG u IgM B2GPI, IgG u IgM AnV, IgG Pr, IgG u IgM Eth antibodies in the II trimester, maintainante of the levels or more decreasing in the Ill trimester. 3. Increasing of lgM PS in the II and more increasing in the Ill trimester. All of these changes have no significant values (p > 0,05). In 10/16 we found extreme values of different antibodies, but all of them had normal delivery.
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PMID:[Antibodies against phospholipids in patients with normal pregnancy]. 2380 53


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