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)

Lupus anticoagulants are a group of antibodies commonly found in patients with autoimmune diseases such as systemic lupus erythematosus. Lupus anticoagulants inhibit phospholipid dependent coagulation and may bind to negatively charged phospholipids. Recent studies have suggested an association between anti-beta 2-glycoprotein I and a lupus anticoagulant, whose activity is frequently dependent on the presence of beta 2-glycoprotein I. Based on these observations, the effect of anti-beta 2-glycoprotein I on the autoactivation of factor XII in plasma was investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited by immunoaffinity purified anti-beta 2-glycoprotein I. The dose-response curve of anti-beta 2-glycoprotein I was identical with that of a precipitating antibody, showing no inhibition at low and high antibody dilutions and maximal inhibition at an intermediate dilution. At high antibody concentrations, an increased rate of factor XIIa activation was observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of beta 2-glycoprotein I as in the plasma itself. This confirms the inhibitory effect of beta 2-GP-I on the contact activation and shows that inhibition is effective on the autoactivation of factor XII in plasma. The inhibitory action of beta 2-glycoprotein I was independent of the inhibition caused by the anti-beta 2-glycoprotein I/beta 2 glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivation by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. The inhibition caused by the antibody is suggested to be caused by a reduced availability of negatively charged phospholipids due to the binding of the anti-beta 2-GP-I/beta 2-GP-I complex. This complex may be a lupus anticoagulant.
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PMID:Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. 748 6

beta 2-glycoprotein I (beta 2-GP-I) the plasma cofactor for anti-phospholipid antibodies adheres on the endothelial surfaces and can be recognized by anti-beta 2-GP-I antibodies naturally occurring in patients with the anti-phospholipid syndrome. As for the cofactor binding to cardiolipin- or gamma irradiated-plates, the endothelial binding is mediated by the so-called phospholipid binding site, a cationic structure able to react with anionic molecules. Endothelial monolayers appear to represent a substrate able to bind beta 2-GP-I and to present it in a suitable manner in order to allow the binding of anti-beta 2-GP-I beta 2 antibodies. The complex between beta 2-GP-I and the respective antibodies induce an endothelial cell activation as demonstrated by the up-regulation of adhesion molecule expression, the secretion of proinflammatory cytokines and the modulation of arachidonic acid metabolism. Taken together these findings strongly sustain a pivotal role for beta 2-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.
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PMID:Modulation of endothelial cell function by antiphospholipid antibodies. 890 79

Antiphospholipid antibodies (aPL) are immunoglobulins of IgG, IgM and IgA isotypes that target phospholipid (PL) and/or PL-binding plasma proteins. Detection of aPL in the laboratory is done currently by both immunoassays and functional coagulation tests. Convention defines aPL specificity in immunoassays according to the particular PL substrate present, for example aPS represents antiphosphatidylserine antibodies. This may be technically incorrect inasmuch as a particular PL may be responsible for binding and highly concentrating a specific plasma protein, the latter then becomes the target for the aPL. The binding of beta(2)GP-I (apolipoprotein H) to the negatively charged PL, cardiolipin (CL) provides a good example of this circumstance. In contrast, aPL which specifically prolong coagulation times in in vitro are called lupus anticoagulants (LA). The precise PL target(s) of the aPL responsible for LA activities are unknown and often debated. The persistent finding of aPL in patients in association with abnormal blood clotting and a myriad of neurological, obstetrical and rheumatic disorders often compounded by autoimmune diseases has led to an established clinical diagnosis termed antiphospholipid syndrome (APS). The common denominator for these APS patients is the presence of circulating aPL on two or more occasions and the observation of events attributable to abnormal or accelerated blood clotting somewhere in vivo. The purpose of this review is to collect, collate, and consolidate information concerning aPL.
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PMID:Antiphospholipid antibodies: discovery, definitions, detection and disease. 1268 18