Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the clinical significance of IgG phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in patients with SLE. The study population consisted of 140 patients with SLE. Sera were examined for IgG phospholipid-dependent anti-beta 2-GPI antibodies by ELISA. IgG phospholipid-dependent anti-beta 2-GPI antibodies were detected in 21 of 140 patients (15%) and remained positive from 4 to 98 months. Significantly higher incidences of thrombosis, intrauterine fetal loss, thrombocytopenia, patients with antiphospholipid syndrome (APS), prolonged APTT, BFP-STS and hemolytic anemia were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies. Moreover, significantly lower incidences of malar rash and serositis were found in SLE patients with phospholipid-dependent anti-beta 2-GPI antibodies, and the majority of these patients satisfied four or five of the revised criteria items of the American Rheumatism Association. These differences were not observed when we compared clinical manifestations in anticardiolipin antibody-positive patients with those in antibody-negative patients by conventional ELISA. These results indicated that SLE patients with IgG phospholipid-dependent anti-beta 2-GPI antibodies show an unique form of SLE.
Lupus 1995 Dec
PMID:Clinical significance of phospholipid-dependent anti-beta 2-glycoprotein I (beta 2-GPI) antibodies in systemic lupus erythematosus. 874 70

The binding capacity to cardiolipin and the functional affinity of affinity-purified anticardiolipin (aCL) IgG of patients with autoimmune disease have been compared with those of individuals with malaria and acquired immunodeficiency syndrome (AIDS). The binding of autoimmune IgG aCL was enhanced gradually by the incorporation of increasing amounts of beta 2-glycoprotein I (beta 2GPI) into the assay, in contrast to that of patients with infectious diseases. In addition, there were significant reductions of functional affinity in autoimmune disease, but not in malaria or in AIDS. These results indicate that beta 2GPI requirement for binding to the target antigen varies inversely with functional affinity in autoimmune disease when beta 2GPI was present, and suggest that IgG aCL are more heterogeneous in this type of disorder than in patients with infectious disease.
Lupus 1995 Dec
PMID:Role of beta 2-glycoprotein I in the anticardiolipin antibody affinity for phospholipid in autoimmune disease. 874 71

NZW x BXSB F1 mice develop a systemic autoimmune syndrome with various lupus-like manifestations. Male animals develop a degenerative coronary disease with myocardial infarction, resulting in death before 6 mo of age. The presence in these mice of anti-phospholipid Abs reacting with beta2-glycoprotein I may contribute to the pathogenesis of the cardiovascular lesions. beta2-glycoprotein I, a plasma protein implicated in various aspects of the coagulation pathway, is also the target of autoantibodies in humans with the anti-phospholipid syndrome. We obtained several mAbs from NZW x BXSB F1 mice that were selected for binding to cardiolipin. Two mAbs are specific for beta2-glycoprotein I and display a species-dependent pattern with preferential reactivity to mouse beta2-glycoprotein I. The other mAbs display charge-mediated interactions with anionic phospholipids in the absence of beta2-glycoprotein I. The analysis of the V region sequences of the mAbs suggests that cationic residues in the H chain complementarity-determining region 3 are important for their phospholipid reactivity. The structural features of the V(H)-D-J(H) junctions of these mAbs further support the view that an increased frequency of unusual V(D)J rearrangements directly contributes to the development of murine autoimmunity.
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PMID:Monoclonal antibodies from NZW x BXSB F1 mice to beta2 glycoprotein I and cardiolipin. Species specificity and charge-dependent binding. 878 29

In order to determine the prevalence and clinical significance of beta 2-GPI-dependent anticardiolipin antibodies (beta 2-GPI/aCL) in patients with systemic sclerosis (SSc), serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 120 healthy control subjects were examined by ELISA using purified beta 2-GPI. IgG isotype beta 2-GPI/aCL was present in eight of 80 patients with SSc (10%), and the presence of beta 2-GPI/aCL IgG was significantly correlated with the presence of isolated pulmonary hypertension (PH). Furthermore, levels of beta 2-GPI/aCL IgG were significantly correlated with levels of mean pulmonary arterial pressure. These data suggest that IgG isotype beta 2-GPI/aCL might be a serological indicator of the severity of PH in patients with SSc.
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PMID:Measurement of anticardiolipin antibodies by ELISA using beta 2-glycoprotein I (beta 2-GPI) in systemic sclerosis. 880 37

The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important.
Lupus 1996 Oct
PMID:Functional effects of anticardiolipin antibodies. 890 63

Cardiolipin binding of IgG-class anticardiolipin antibody (aCL) depends on the existence of beta 2-glycoprotein I (beta 2-GPI). We developed an EIA system that enables detection of antibodies against beta 2-GPI, without the presence of cardiolipin. This system involves use of irradiated polystyrene plates, in which oxygen atoms are introduced onto the surfaces of the plates. beta 2-GPI bound to the surface of these plates is assumed to undergo a conformational change that exposes normally cryptic epitopes. Anti-beta 2-GPI antibody measured using this EIA system showed good correlation with aCL measured by conventional EIA methods and may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE. Utilizing this EIA system and beta 2-GPI-deleted mutants, we found that the fourth domain of beta 2-GPI is involved in expression of one of the cryptic epitopes recognized by aCL. We also found that oxidized LDL are sequentially targeted by beta 2-GPI and aCL.
Lupus 1996 Oct
PMID:Anti-beta 2-glycoprotein I antibody: specificity and clinical significance. 890 64

Antiphospholipid' (aPL) antibodies are of important clinical significance because of their association with thrombosis both arterial and venous, recurrent foetal loss, specific neurological sequelae like seizures and chorea, cardiac valvular abnormalities and thrombocytopenia. Traditionally these autoantibodies have been assayed using phospholipid (PL) dependent tests and are classified as lupus anticoagulants (LA) and anticardiolipin (aCL) antibodies based on the method of detection. The antibodies thus, had been thought to bind PLs but it has now become clear that the true antigens are PL-binding proteins. The major protein consistently found as the target antigen for these autoantibodies is beta 2-glycoprotein I (beta 2-GPI). Other candidate PL-binding proteins have also been investigated including prothrombin, protein C and protein S but thus far appear to play less important roles in the binding of these antibodies.
Lupus 1996 Oct
PMID:beta 2-Glycoprotein I: target antigen for autoantibodies in the 'antiphospholipid syndrome'. 890 65

The Antiphospholipid Syndrome is defined by the association between peculiar clinical manifestations, namely arterial and/or venous thrombosis, recurrent abortions and thrombocytopenia, and the antiphospholipid antibodies. These antibodies are directed to plasma proteins bound to anionic phospholipids or other anionic surfaces: so far, beta 2-glycoprotein I is the best known and characterized antiphospholipid 'cofactor' (this issue is specifically treated in other parts of this journal). In recent years, such a role has been reported also for prothrombin, activated Protein C, Protein S, Annexin V, Thrombomodulin, high- and low-molecular weight kininogens. Anti-prothrombin antibodies are detected in approximately 50% of the antiphospholipid-positive patients; conversely, limited data are available regarding the prevalence the other antibodies. 'Cofactors' are necessary for the expression of both the immunological and the functional properties of their respective antiphospholipid antibodies. In particular, the recognition of the calcium-mediated prothrombin/lipid complex by anti-prothrombin antibodies hampers prothrombin activation, thus causing the prolongation of the phospholipid-dependent coagulation reactions. The interaction between antiphospholipid antibodies and natural inhibitors of coagulation such as activated Protein C, its non-enzymatic accessory protein Protein S or Thrombomodulin might increase the risk to develop thromboembolic events. Similarly, the presence of antibodies to surface-bound Annexin V has been hypothesized to play a role in recurrent abortions and fetal deaths. However, to clearly establish whether and which antiphospholipid antibodies represent risk factors for the thromboembolic events of the antiphospholipid syndrome, further studies of their behaviour and properties as well as the identification and characterization of (possibly) other antibodies are required.
Lupus 1996 Oct
PMID:Non beta 2-glycoprotein I cofactors for antiphospholipid antibodies. 890 67

Most autoantibodies associated with the antiphospholipid (aPL) syndrome and detected in standard anticardiolipin and/or lupus anticoagulant assays are directed against beta 2-glycoprotein I (beta 2-GPI) or prothrombin. Recent data indicate that these antibodies can also be detected in immunoassays utilizing purified protein antigens, in the absence of phospholipids. Initial clinical studies suggest that positivity in anti-beta 2-GPI immunoassays is more closely associated with the clinical manifestations of the aPL syndrome than is positivity in conventional anticardiolipin ELISAs. Anti-beta 2-GPI immunoassays may detect certain anti-beta 2-GPI antibodies that are not detectable in conventional anticardiolipin assays, but do not detect authentic (beta 2-GPI-independent) anticardiolipin antibodies. It appears that the former, but not the latter, antibodies are associated with the clinical manifestations of the aPL syndrome. The potential advantages and disadvantages of these new immunoassays in the clinical evaluation of the aPL syndrome are discussed.
Lupus 1996 Oct
PMID:Antigenic specificities of antiphospholipid autoantibodies: implications for clinical laboratory testing and diagnosis of the antiphospholipid syndrome. 890 74

The family of antiphospholipid antibodies includes antibodies binding to cardiolipin in serological test for syphilis, antibodies prolonging the clotting time in lupus anticoagulant test, antibodies reacting with plasma phospholipid-binding proteins, such as beta 2-glycoprotein I and prothrombin, and antibodies binding to oxidized low-density lipoprotein (LDL). Antiphospholipid antibodies are traditionally associated with arterial and venous thrombosis in patients with primary or secondary antiphospholipid syndrome. The recent studies, especially those on patients with myocardial infarction, extend the concept of antiphospholipid antibodies, and suggest that they play a role also in atherosclerosis. Based on the clinical studies and immunological findings, it seems that the differences in the specificity of antiphospholipid antibodies may reflect to their pathogenetic mechanisms and, finally, to their clinical consequences. The present review suggests that antibodies to oxidized LDL may not interfere directly with blood coagulation, but seem to have importance in the inflammation of the vessel wall in atherosclerosis and in vasculitis. Instead, antibodies to beta 2-glycoprotein I and to prothrombin show a closer association with thrombosis. It is possible that in the atherosclerotic plaque, the plasma proteins, such as beta 2-glycoprotein I or prothrombin, are bound to the endothelial surface and antibodies to cryptic epitopes revealed in these proteins are induced. These antibodies may contribute to the formation of atherosclerotic thrombosis by changing the balance of haemostasis toward hypercoagulative state.
Lupus 1996 Oct
PMID:Antiphospholipid antibodies and atherosclerosis. 890 78


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