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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-phospholipid antibodies (aPL), in the form of anti-cardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC), are found in a number of disorders, including systemic lupus erythematosus. Autoimmune aPL are associated with clinical manifestations that may include vascular thrombosis, recurrent fetal loss, thrombocytopenia, livedo reticularis and neurological abnormalities. aPL found in the context of infections such as syphilis are not usually associated with clinical complications. Here we report the presence of aCL in Brown Norway (BN) rats treated with mercuric chloride (HgCl2), which is known to induce a number of other autoantibodies. Some also showed LAC activity as shown by extension of the kaolin clotting test time. The binding of human autoimmune aPL is known to be considerably enhanced by a serum cofactor, beta 2-glycoprotein I; only slight enhancement, and in some cases inhibition, was found with BN rat aPL. These results indicate that aPL can be added to the list of autoantibodies that have been documented in the HgCl2 treated BN rat. The effect of addition of serum co-factor suggests that these are most closely related to human infection-associated (as opposed to autoimmune) aPL.
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PMID:Anti-phospholipid antibodies in the mercuric chloride treated brown Norway rat. 798 Aug 48

Recent evidence suggests that lupus anticoagulants are immunologically distinct from the anticardiolipin antibodies. Nevertheless, the associated clinical complications exhibited by the two groups of antibodies are similar. They have been shown to have a strong association with a history of arterial and venous thrombosis, thrombocytopenia and neurological disease in patients with SLE or lupus-like disorders. The association between antiphospholipid antibodies and recurrent fetal loss is suggested by the currently available data but is not firmly established. Patients with lupus and antiphospholipid antibodies and an established history of recurrent fetal wastage are at high risk for experiencing subsequent fetal loss, but it is not yet known whether the same is true for patients without a history of fetal loss. The association of thrombosis, neurological disease, thrombocytopenia, and fetal loss in patients with non-SLE disorders has not been as extensively studied. Only recently have investigators such as Ginsberg and colleagues begun to show in prospective studies that there may, in fact, be a statistically significant risk of thrombotic events in otherwise healthy individuals with antiphospholipid antibodies. Many of the diverse minor manifestations reported in individual patients, case series, or cross-sectional studies such as livedo reticularis, leg ulcers, and hemolytic anemia may, alternatively, be due to coincidence or chance. Efforts to elucidate the mechanisms of thrombosis in patients with antiphospholipid antibodies is an area of active research. Most efforts have been based on the effects of these antibodies on endothelial cell and platelet function as well as on the fibrinolytic system. In addition, it has recently been shown that binding of antiphospholipid antibodies to phospholipids requires the serum "co-factor" beta 2-glycoprotein I. In patients with SLE selected for the presence of the lupus anticoagulant, thrombosis, or fetal loss, Viard and associates found that 17 of 47 (36%) patients had anti-beta 2-glycoprotein I antibodies. They were able to show, in their small retrospective study, that there was an association between the presence of these antibodies and anticardiolipin activity, lupus anticoagulant activity, and thrombotic events, but not with spontaneous abortion. Of patients with SLE and thrombosis (9 of 47) eight of nine were positive for anti-beta 2-glycoprotein I antibodies, seven of nine were positive for anticardiolipin antibodies, and eight of nine were positive for the lupus anticoagulant. The known inhibitory effect of beta 2-glycoprotein I on platelet aggregation, on platelet prothrombinase activity, and on the intrinsic pathway of coagulation supports the hypothesis that implicates beta 2-glycoprotein I in the pathogenesis of unwanted thrombotic events.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical syndromes associated with lupus anticoagulants. 805 30

Lupus anticoagulants are antibodies that inhibit phospholipid dependent coagulation reactions in vitro. These antibodies are of clinical interest because of their association with a variety of clinical manifestations characterized by microvascular thrombosis. Although these antibodies were originally thought to be directed at negatively charged phospholipid, recent studies have suggested that they may be directed at phospholipid-protein complexes. The effect of antibodies directed against beta 2-glycoprotein I (beta 2-GP I, apolipoprotein H) on phospholipid-dependent coagulation reactions has been studied. Polyclonal and monoclonal antibodies to beta 2-GP I were found to inhibit thrombin generation in a dose dependent manner. Inhibition of thrombin formation was due to specific interaction with beta 2-GP I. There was no evidence that inhibition was due to crossreactivity with other proteins involved in the prothrombinase complex. These findings document that antibodies directed against beta 2-GP I can have anticoagulant activity analogous to lupus anticoagulant activity and are consistent with the recent observation of such activity in lupus anticoagulant patient samples.
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PMID:Antibodies to beta 2-glycoprotein I inhibit phospholipid dependent coagulation reactions. 811 86

We present functional and binding data relevant to the reported roles for prothrombin and beta 2-glycoprotein I (beta 2GPI) in the expression of lupus anticoagulant activity. In a purified system containing human prothrombin, Xa, Va, and a rate-limiting concentration of phosphatidylserine (PS)/phosphatidylcholine (PC) vesicles, the preliminary incubation of vesicles with protein A separated IgG preparations from 10 lupus anticoagulant plasmas, calcium, and prothrombin enhanced the inhibitory effect of all IgG preparations upon thrombin generation. Experiments in a purified factor X activation system provided supporting data that a similar preliminary incubation with prothrombin enhanced the inhibitory effect of many of the IgG preparations upon factor X activation. However, we could not obtain unequivocal evidence that prothrombin was an obligatory cofactor for lupus anticoagulant IgG to inhibit procoagulant phospholipid function, because lupus anticoagulant IgG separated by protein A chromatography contained traces of prothrombin. The binding of many IgG preparations to immobilized PS was enhanced by prothrombin when calcium ions were present. beta 2GPI enhanced binding of many of the IgG preparations to immobilized PS both in the presence and absence of calcium, yet beta 2GPI failed to enhance the ability of the IgG preparations to inhibit phospholipid function in purified prothrombin and factor X assays. Moreover, the IgG preparations prolonged the dilute Russell's viper venom time (dRVVT) of beta 2GPI-depleted normal plasma. Nine of 10 IgG preparations bound to prothrombin on Western blots in the absence of calcium and phospholipid, whereas no preparation bound to beta 2GPI. Passage of five citrated lupus anticoagulant plasmas through a prothrombin affinity column in the absence of added calcium and phospholipid removed most of the activity prolonging the dRVVT of normal plasma, and IgG in the pass-through plasma no longer bound to PS in the presence of prothrombin and calcium ions. IgG in prothrombin column eluates had strikingly enhanced specific lupus anticoagulant activity and also specific PS binding activity in the presence of prothrombin and calcium ions. Thus, lupus anticoagulant plasmas were shown to contain IgG binding to prothrombin, in the absence of calcium ions and phospholipid, which could also, in the presence of calcium ions and prothrombin, bind to PS and express lupus anticoagulant activity.
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PMID:Functional and binding studies of the roles of prothrombin and beta 2-glycoprotein I in the expression of lupus anticoagulant activity. 818 Mar 83

We studied whether or not an anti-beta 2-glycoprotein I antibody (aGPI) had lupus anticoagulant-like activity, employing the diluted Russel viper venom time (dRVVT) and kaolin clotting time (KCT) as indices. aGPI prolonged the dRVVT and KCT of beta 2-glycoprotein I (GPI)-depleted normal plasma in the presence of extrinsic GPI. This prolongation of the dRVVT and KCT occurred immediately after the addition of aGPI and GPI, and was subsequently enhanced further in a time-dependent manner. The GPI/aGPI combination was judged to have lupus anticoagulant-like activity by the dRVVT-platelet neutralization test, but this was not confirmed by a lupus anticoagulant-specific test, i.e., the activated partial prothrombin time (APTT) using hexagonal phospholipid. From these findings, it can be concluded that aGPI has lupus anticoagulant-like activity in the presence of GPI, but may be a partially or considerably different antiphospholipid antibody from lupus anticoagulant. Further investigations may be needed to clarify this point.
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PMID:Anticoagulant activity of an anti-beta 2-glycoprotein I antibody is dependent on the presence of beta 2-glycoprotein I. 748 88

Antiphospholipid antibodies, defined either by lupus anticoagulant (LA) activity or positive anticardiolipin immunoabsorbent assay (ACA) are associated with a predisposition to thromboses, recurrent fetal loss or thrombocytopenia. The mechanisms for these predispositions remain undefined. We have enriched immunoglobulin fractions from two patient plasmas to obtain antibodies with LA activity but no ACA, or conversely, with ACA positivity but no LA, in order to investigate in vitro characteristics which might explain a thrombotic propensity. beta 2-glycoprotein I (beta 2-GPI), the plasma cofactor required for ACA binding to negatively charged phospholipid, has previously been shown to inhibit prothrombinase generation in the presence of activated platelets (8). We now report that beta 2-GPI, at physiological concentrations, inhibits the generation of factor Xa in the presence of activated gel-filtered platelets. Further, ACA interferes with this inhibition, resulting in protracted, unopposed factor Xa generation. This interference with beta 2-GPI, a natural anticoagulant component of plasma, is potentially prothrombotic. LA immunoglobulins behave differently and inhibit factor Xa generation in a manner similar to beta 2-GPI. These findings provide the basis for a previously unsuspected mechanism for thrombosis in patients with aPL.
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PMID:Anticardiolipin antibodies block the inhibition by beta 2-glycoprotein I of the factor Xa generating activity of platelets. 805 75

We investigated whether anticardiolipin antibody (aCL), which is common in patients with end-stage renal disease (ESRD), was dependent on beta 2-glycoprotein I (GPI), a cofactor of aCL. Lupus anticoagulant (LA) was identified in 13/39 hemodialysis (HD) patients. GPI-independent aCL was positive in 12/39 of this group, five of whom had both GPI-independent aCL and LA. Three of the 20 patients on symptomatic and supportive treatment other than HD had LA, but none of them were aCL positive. When GPI was added to the assay system to allow for GPI-dependent aCL measurement, the optical density (OD) readings of 10/12 HD patients decreased, thus proving that they were negative for aCL. In contrast, the OD readings of 6 control patients with systemic lupus erythematosus (SLE) increased markedly (3/6) or decreased slightly to moderately (3/6), however, within the limits of positive range, indicating GPI-dependent cCL positivity. These results suggested that LA and GPI-independent aCL were produced in ESRD patients, especially those on HD, possibly through mechanisms related to the hemodialysis membrane. However, the significance of GPI-independent aCL in this clinical setting, which may differ from the GPI-dependent aCL detected in SLE patients, as well as the possible participation of serum GPI in the production of aCL remain to be clarified.
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PMID:beta 2-Glycoprotein I-dependent and-independent anticardiolipin antibody in patients with end-stage renal disease. 830 48

In some individuals, the presence of antibodies to negatively charged phospholipids, currently measured as the lupus anticoagulant, and anticardiolipin antibodies is associated with certain clinical features, particularly a predisposition to both arterial and venous thromboses, thrombocytopenia, and spontaneous abortion. This syndrome is seen in patients with systemic lupus erythematosus (SLE). However, methods for measuring anticardiolipin antibody, especially epitope of anticardiolipin antibody which is not considered cardiolipin itself, but rather a complex of cardiolipin and beta 2-glycoprotein I are not well defined. Although many hypotheses have been proposed to explain the relation between antiphospholipid antibodies and thrombosis, the pathogenesis of thrombosis remains unclear. In this article, some problems in assaying anticardiolipin antibody, characteristics of antiphospholipid antibodies and the clinical significance of these antibodies are reviewed and discussed.
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PMID:[Assay of anticardiolipin antibodies and its clinical significance]. 837 1

We investigated the prevalence of various autoantibodies [anti-cardiolipin antibody (aCL), lupus anticoagulant (LA), immune complexes (ICs), anti-nuclear antibody (ANA), and anti-deoxyribonucleic acid antibody (aDNA)] in hemophiliac individuals with (n = 50) and without (n = 42) infection by human immunodeficiency virus type 1 (HIV-1). The positivity rate for ANA was similar in both groups, and none of the patients was positive for LA and aDNA. aCL was positive in 35 of 50 (70%) HIV-1-positive hemophiliac individuals and 33 of 42 (79%) HIV-1-negative hemophiliac individuals. However, the majority of the aCL was revealed to be beta 2-glycoprotein I independent, thus corresponding to a syphilis type aCL that does not cause the so-called antiphospholipid syndrome. A total of 39 of the 45 HIV-1 positive hemophiliac individuals (87%) and 34 of 41 HIV-1-negative hemophiliac individuals (83%) had at least one type of IC [C1q-, C3d-, and/or murine monoclonal rheumatoid factor (mRF)- IgG]. The mechanism producing various autoantibodies in hemophiliac persons irrespective of their HIV-1 status is still unclear, but pathogens (e.g., HIV-1, hepatitis B, and hepatitis C) and alloantigens in the blood products that these patients require may be possible candidates. The clinical significance of the presence of these autoantibodies and the underlying mechanisms involved both need to be clarified further.
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PMID:High prevalence of anti-cardiolipin antibody, C1q-, C3d-, and mRF-IgG immune complexes, and anti-nuclear antibody in hemophiliacs irrespective of infection with human immunodeficiency virus type 1. 841 Jun 68

Antiphospholipid (aPL) antibodies are of major interest not only because the lupus anticoagulant (LA) causes an inhibition of in vitro blood coagulation, but also because the presence of aPL antibodies confers a risk of thrombosis. The inhibition of in vitro phospholipid-dependent coagulation (LA) is thought to be caused by the binding of LA to procoagulant phospholipid surfaces, thus impeding the clotting process. Another class of aPL antibodies are those originally described to be directed against negatively charged phospholipids, in particular cardiolipin (ACA). ACA are usually directed against a complex antigen consisting of negatively charged phospholipid and a plasma protein, beta 2-glycoprotein I (beta 2-GPI). Further, there is antibody heterogeneity even within individual patients so that ACA and LA are separable using physicochemical techniques such as ion exchange chromatography and chromatofocusing. Using such techniques we have enriched Ig fractions for LA and ACA from two patient plasmas. The majority of Ig with LA activity had a pI of 7.2 to 7.3 whereas ACA had a pI of 5.0 to 5.2. Using these enriched fractions labeled with [125I]-iodine we have shown that LA binds to platelets in a specific and saturable manner. Binding is dependent on thrombin activation. [125I]-ACA behaves differently. Like LA, binding is specific and dependent on thrombin activation but in this case requires the presence of beta 2-GPI. ACA, in the presence of beta 2-GPI, competes for binding with LA suggesting the same or contiguous site. There is no cross-reactivity of these antibodies with GPIIb/IIIa and the most likely binding site is phospholipid. In neither case does LA nor ACA have an effect on thrombin-induced release of serotonin or beta-thromboglobulin nor do they affect platelet aggregation induced by a number of agonists. This antibody binding may play an etiological role in thrombocytopenia associated with aPL, but does not explain thrombosis on the basis of hyperaggregability or increased platelet release.
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PMID:Beta 2-glycoprotein I is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants. 844 87


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