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)

Anticardiolipin antibodies (aCL) purified from patients with autoimmune disease have recently been shown to interact with a phospholipid-binding plasma protein, beta 2-glycoprotein I (beta 2-GPI). The aim of this study was to determine whether aCL purified from patients with infection also interact with beta 2-GPI. aCL purified from 23 patients with malaria, infectious mononucleosis, tuberculosis, hepatitis A or syphilis did not require the presence of beta 2-GPI to bind cardiolipin (CL). In contrast, aCL were purified from 11 out of 12 patients with autoimmune disease that bound CL only in the presence of beta 2-GPI. Thrombotic complications appear to be associated with aCL occurring in autoimmune disease but not with aCL associated with infections. We postulate that this increased risk of thrombosis in the autoimmune group may be due to the presence of aCL that bind CL in association with beta 2-GPI, a plasma protein with anticoagulant activity.
Lupus 1992 Feb
PMID:A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. 130 67

Although autoimmune antiphospholipid antibodies (aPL) may require a serum cofactor, beta 2-glycoprotein I (beta 2GPI), for maximal binding in aPL ELISA, it is not known whether cofactor is absolutely required or is merely an enhancing factor for binding, nor is it clear whether aPL bind to cofactor itself, a cofactor-lipid complex, or a phospholipid modified in some way by cofactor. We therefore isolated and purified beta 2GPI and evaluated its relationship to both IgG and IgM aPL binding. aPL derived from different sera appear to have differing requirements for cofactor; the proportion of total binding attributable to cofactor varies from 46% to 95%. aPL do not bind to beta 2GPI in the absence of phospholipid. Enhanced binding to phospholipid is seen if beta 2GPI is provided either before or with the test antibody. Autoimmune aPL bind phospholipid better with human rather than bovine cofactor. The requirement for cofactor is greater for low-avidity aPL as measured in an IgG-human cofactor system. Cofactor requirement alone does not predict the presence or absence of associated clinical complications.
Lupus 1992 Feb
PMID:Antiphospholipid antibodies differ in aPL cofactor requirement. 130 68

Anticardiolipin antibodies (aCL) were recently discovered to recognize a complex consisting of phospholipids and apolipoprotein H (apo H). In this study, we determined the serum apo H levels in 36 systemic lupus erythematosus (SLE) patients with or without antiphospholipid antibodies (aPL), including aCL and lupus anticoagulants, to clarify the possible effects of aPL on apo H levels in vivo. The apo H levels were low in SLE patients as compared with 22 healthy controls. However, no associations were found between apo H levels and circulating aPL or clinical features of the antiphospholipid antibody syndrome. A secondary hyperlipidemic state, which probably related to lupus nephritis (proteinuria) and/or prednisolone treatment, increased apo H levels in SLE patients.
Lupus 1992 May
PMID:Serum apolipoprotein H levels in systemic lupus erythematosus are not influenced by antiphospholipid antibodies. 130 75

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

A group of anticardiolipin antibodies (aCL) require beta 2-glycoprotein I (beta 2GPI) to recognize their target, which might be located on endothelial cells (EC) and/or platelets. Following incubation with epithelial cells, 13 of 30 lupus sera retained EC-reactive antibodies of the IgG, IgA and IgM isotypes. Associated aCL and anti-phosphatidylethanolamine antibodies were partly absorbed on eC as well as EC. The former antibodies were more efficiently removed in the presence than in the absence of the latter. The presence of beta 2GPI in the affinity-purified aCL preparations may explain their binding to EC, as this cross-reaction was abrogated by the removal of the cofactor and restored by its re-introduction. Seventy four per cent of EC were faintly stained with polyclonal or monoclonal antibody directed to the cofactor. The beta 2GPI mediated aCL binding to EC membranes could this be influential in the development of thrombosis and/or thrombocytopenia in aCL-positive patients.
Lupus 1995 Jun
PMID:Role of beta 2-glycoprotein I in the antiphospholipid antibody binding to endothelial cells. 765 84

A 26-year-old man with systemic lupus erythematosus (SLE) and a history of acute myocardial infarction developed portal hypertension accompanied by abnormal liver function and esophageal varices. As his clinical course suggested the possibility of antiphospholipid syndrome, a titer of anticardiolipin antibody (aCL) was serially measured using an enzyme immunoassay with beta 2-glycoprotein I as a cofactor. The titer of aCL increased with the development of portal hypertension, and promptly decreased with the improvement of liver function just after corticosteroid therapy. The long-term course in this case suggests that aCL may cause portal hypertension associated with SLE.
Lupus 1995 Jun
PMID:Portal hypertension associated with anticardiolipin antibodies in a case of systemic lupus erythematosus. 765 97

We studied the effect of beta 2-GPI on binding of antibodies in sera from patients with leprosy and patients with the antiphospholipid syndrome (APS) to CL in enzyme-linked immunosorbent assays (ELISAs). Increased levels of IgG aCL were detected in 59 of 61 leprosy patients' sera by the standard aCL-ELISA in the presence of bovine beta 2-GPI and in 60 of the 61 leprosy patients' sera by the modified aCL-ELISA without beta 2-GPI. When tested by both aCL-ELISAs on the same plate, 10/31 leprosy sera and 9/10 APS sera bound better in the standard aCL-ELISA, 16/31 leprosy sera bound better in the modified aCL-ELISA and in five leprosy and one APS sera the difference was not significant. A dose-dependent enhancing effect of beta 2-GPI on the leprosy and APS sera binding to CL was confirmed using purified human beta 2-GPI. Enhanced binding was seen if beta 2-GPI was added either before or together with the test serum. In 11/61 leprosy sera increased levels of IgG antibodies against beta 2-GPI were found by ELISA. Leprosy anti-beta 2-GPI antibodies appear to be a separate antibody population recognizing only beta 2-GPI adsorbed on the ELISA plate. These results demonstrate heterogeneity of leprosy aCL with respect to their beta 2-GPI requirement for binding to CL.
Lupus 1994 Dec
PMID:Anticardiolipin antibodies in infections are heterogenous in their dependency on beta 2-glycoprotein I: analysis of anticardiolipin antibodies in leprosy. 770 10

We investigated the clinical significance of IgG beta 2-glycoprotein I (GPI)-dependent anticardiolipin antibodies (aCL) in rheumatic diseases. Three hundred and seventeen patients were entered. They consisted of 133 patients with SLE, 60 with RA, 45 with SSc, 37 with PM, 23 with overlap syndrome (overlap), and 19 with unclassified connective tissue disease (UCTD). IgG beta 2-GPI-dependent aCL were examined by ELISA. While IgG beta 2-GPI-dependent aCL were detected in 13% of patients with SLE, these aCL were positive in two patients with SSc, two with overlap and 14 with UCTD. A significant association between IgG beta 2-GPI-dependent aCL and thrombosis was found. Clinical manifestations were studied in 32 patients with secondary APS based on SLE and 14 with primary APS (PAPS). Incidence of malar rash, arthritis, renal disorder, leucopenia, immunological disorders and hypocomplementemia were significantly less frequent in patients with PAPS. IgG beta 2-GPI-dependent aCL were detected in all patients with PAPS and in 34% of secondary APS. This difference was significant. These data suggest that IgG beta 2-dependent aCL are useful for identifying a subset in patients with APS.
Lupus 1995 Feb
PMID:Disease distribution of beta 2-glycoprotein I-dependent anticardiolipin antibodies in rheumatic diseases. 775 7

beta 2-Glycoprotein I (beta 2-GPI) is a cofactor in the recognition of a phospholipid antigen, cardiolipin, by anticardiolipin antibodies in autoimmune diseases such as systemic lupus erythematosus. We examined the interaction of various forms of bovine beta 2-GPI, such as its intact form, desialylated form (Asialo beta 2-GPI), N-terminal domain (domain I) and the modified forms of beta 2-GPI and Asialo beta 2-GPI with nicks in their C-terminal domains (domain 5), with phospholipid liposomes under different conditions of pH and ionic strength. We found that at neutral pH and low ionic strength beta 2-GPI bound to liposome membranes containing cardiolipin with a dissociation constant (Kd) of 10(-8) M. Phosphatidylglycerol, phosphatidylserine, phosphatidic acid or phosphatidylinositol bound to beta 2-GPI, but phosphatidylcholine did not. We also found that domain I and Asialo beta 2-GPI bound to cardiolipin with Kd values of 10(-6) and 10(-8) M, respectively. At neutral pH and both low and high ionic strengths, the affinities of nicked forms of beta 2-GPI and Asialo beta 2-GPI for cardiolipin were lower than those of intact forms but similar to that of domain 1.
Lupus 1995 Feb
PMID:Structure and function of beta 2-glycoprotein I: with special reference to the interaction with phospholipid. 775 8

Anticardiolipin (aCL) and anti-beta 2-glycoprotein I(anti beta 2GPI) antibodies have been shown in animal models as not cross-reacting antibody populations. This observation prompted us to prove if anti-beta 2GPI exist in human sera by using a reliable method and then to investigate if these are independent from aCl antibodies. We have developed a new ELISA for the detection of anti-beta 2GPI antibodies employing the coating of the protein in carbonate buffer to irradiated microtitre plates and the filtration of serum samples, that makes irrelevant the binding to the uncoated wells. IgG F(ab)2 fragments from IgG positive sera were shown bind beta 2GPI, providing that the binding was a specific antibody binding, mediated by the antigen binding site of the antibody molecule: moreover the antibodies were not able to differentiate native and delipidated beta 2GPI coated plates, making a possible role of a phospholipid contaminant unlikely. On the other hand, the phosphorus content of native as well as delipitated beta 2GPI was undetectable. IgG, but not IgM, anti-beta 2GPI antibodies were classically inhibited by the addition of soluble beta 2GPI, while cardiolipin liposomes appear to modify the reaction in a completely different way, possibly by the described interaction between cardiolipin and beta 2GPI.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupus 1995 Apr
PMID:Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome? 779 15


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