Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.
Lupus 2002
PMID:Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies. 1247 4

Beta2-glycoprotein I (beta2-GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported (J. Lipid Res., 42: 697, 2001; J. Lipid Res., 43: 1486, 2002) that beta2-GPI specifically binds to Cu2+-oxidized LDL (oxLDL) and that the beta2-GPI ligands are omega-carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with beta2-GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the omega-carboxyl function of the beta2-GPI ligands was necessary for beta2-GPI binding. The ligand-mediated noncovalent interaction of beta2-GPI and oxLDL undergoes a temperature- and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable beta2-GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence of beta2-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing beta2-GPI or LDL. Thus, the beta2-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis.
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PMID:Circulating oxidized LDL forms complexes with beta2-glycoprotein I: implication as an atherogenic autoantigen. 1256 69

Anti-phospholipid Ab (aPL) are a heterogeneous group of autoantibodies directed against various combinations of phospholipids (PL) and PL-binding proteins. Lupus anticoagulant (LA) Ab, a subset of aPL, exhibit anticoagulant properties in vitro, but are procoagulant in vivo. Most LA Ab are specific for either beta(2)-glycoprotein I (beta(2)GPI) or prothrombin (PT), two PL-binding proteins. We have previously shown that beta(2)GPI and beta(2)GPI-dependent aPL bind specifically to apoptotic, but not viable, thymocytes. In this study, we demonstrate that PT, like beta(2)GPI, binds selectively to the surface of apoptotic, but not viable, Jurkat cells. Furthermore, PT supports the binding of systemic lupus erythematosus-derived polyclonal and murine monoclonal LA Ab to apoptotic cells. Two LA mAb, which differed dramatically in their relative affinities for PT, were studied. Although one mAb (29J3-62) had a high affinity for PT alone, the other (29I4-24) showed minimal reactivity with PT alone and required PL for elevated binding. Monovalent fragments of 29I4-24 reacted with PL-bound PT with high affinity, suggesting that this mAb recognizes a PL-dependent epitope. Despite these differences, PT-dependent binding of both mAb to apoptotic cells was 30-fold greater than that to viable cells. Moreover, binding of PT to apoptotic cells was, itself, increased in the presence of bivalent, but not monovalent, forms of either mAb. In summary, our data demonstrate the following: 1) specific binding of PT to apoptotic cells, an effect enhanced by PT-dependent LA Ab; 2) heterogeneity of PT-dependent LA Ab; and 3) potential pathogenicity of Ab of either low or high affinity for PT.
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PMID:Prothrombin binds to the surface of apoptotic, but not viable, cells and serves as a target of lupus anticoagulant autoantibodies. 1262 2

Thrombotic complications are a significant cause of morbidity and mortality in cancer patients. Studies in Caucasian populations have shown that up to one-third of such patients test positive to antiphospholipid antibodies. Our aim was to determine the prevalence and serotypes of antiphospholipid antibodies in an unselected group of Asian cancer patients with thrombosis. All patients with cancer-related thrombosis seen in the Department of Hematology-Oncology and Radiation Oncology were enrolled in this study. The study period was from April 2000 to May 2001. Antiphospholipid antibodies tests were performed, namely lupus anticoagulant screen, anticardiolipin antibodies (IgG and IgM) and anti-beta-2 glycoprotein I antibodies (B2 GPI) IgG, IgM and IgA. Thirty-three patients were recruited. There were 14 males and 19 females, with an age range of 35-78 years of age. Of those enrolled, there were 25 Chinese, five Malays and three Indians. The patients had several cancer types: 11 (36.7%) patients had adenocarcinoma as the histological cell type. Of the 33 patients, 75.8% had stage IV disease. Arterial thrombosis was seen in eight patients (24.2%), and venous thrombosis occurred in 29 patients (87.9%). Antiphospholipid antibodies were positive in 60.6% of the patients, of which anti-B2GPI IgA antibody was the most prevalent antiphospholipid present (46.9%). The presence of anti-beta-2 glycoprotein I IgA antibody was associated with strokes, extensive and recurrent venous thrombosis, and coincident arterial and venous thrombosis. A high prevalence of antiphospholipid antibodies (60.6%) was found in Asian patients with cancer-related thrombosis. The presence of antiphospholipid antibodies, particularly anti B2GPI IgA, may identify a subset of cancer patients who are at high risk of developing thrombotic complications, and further studies are warranted.
Lupus 2003
PMID:High prevalence of antiphospholipid antibodies in Asian cancer patients with thrombosis. 1263 Jul 55

The laboratory diagnosis of antiphospholipid antibody syndrome currently requires two consecutive positive results in either lupus anticoagulant or anticardiolipin antibody assays. Antibodies against beta-2-glycoprotein I (abeta2-GPI) are suggested as a new marker for the syndrome. The inclusion of abeta2-GPI in the official diagnostic criteria has so far been precluded owing to lack of an international standard and also technical difficulties. Samples from 5367 consecutive patients sent to a national reference laboratory mainly because of various thrombotic events were studied. An IgG abeta2-GPI ELISA assay was performed in addition to lupus anticoagulant (dRVVT and PTT-LA) and IgG anticardiolipin antibody determinations to evaluate patient groups in which the new assay might be of value. From a total of 90 patients, 2.2% of the samples were abeta2-GPI positive; 51 patients had abeta2-GPI as the only positive antiphospholipid antibody marker; 20 patients had had a venous thrombosis and 14 an arterial thrombosis, 4 had pregnancy complications and 2 had thrombocytopenia. Relatively young patients with cerebrovascular ischaemic events seemed especially to present sole abeta2-GPI positivity. The abeta2-GPI positivity remained fairly constant in the 23 patients from whom follow-up samples were taken. It is concluded that the IgG abeta2-GPI assay seems to be a potentially important additional diagnostic tool for the antiphospholipid antibody syndrome.
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PMID:Beta-2-glycoprotein I antibodies in patients with thrombosis. 1275 92

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome (APS). We recently reported that oxidized LDL(oxLDL) is subsequently targeted by beta2-GPI and anti-beta2-GPI auto-Abs and that-carboxyl variants of 7-ketocholesteryl esters, such as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and 7-ketocholesteryl-12-carboxy (keto) octadodecanoate (oxLig-2), are ligands for beta2-GPI (J Lipid Re 2001; 42: 697; J Lipid Res 2002; 43: 1486). These beta2-GPI ligands provide an electrostatic interaction between oxLDL and beta2-GPI followed by forming stable complexes (such as Schiff base adducts). The omega-carboxyl function in these ligand is responsible for beta2-GPI binding to oxLDL and the oxLDL-beta2-GPI complexes are anti-beta2-GPI auto-Ab-dependently taken up by macrophages (i.e., by phagocytosis). Our recent observations are consistent with the evidence that beta2-GPI co-localizes with lymphocytes and mononuclear cells in human athero-plaques. Thus, autoimmune thrombogenesis (atherogenesis) is linked to interaction of anti-beta2-GPI Abs with the beta2-GPI-oxLDL complexes. We propose an alternative idea, that an immune response against the beta2-GPI-oxLDL complexes may be involved in mechanisms in the development of atherosclerosis, which has been explained by the theory of 'the response to injury'.
Lupus 2003
PMID:Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome. 1289 97

Antiphospholipid (aPL) and antiplatelet (aPlt) antibodies, found in patients with autoimmune diseases, are also detected in infectious diseases. The purpose of this study was to examine the prevalence of these antibodies in HIV patients and to evaluate an association of these antibodies with thrombocytopenia and/or thrombosis. Sixty-three HIV-seropositive patients and 52 normal controls were studied. Anti-cardiolipin (aCL), anti-beta(2) glycoprotein I (anti-beta(2)GPI), and antiprothrombin (aPT) antibodies were determined and the lupus anticoagulant (LA) test was performed. Antiplatelet antibodies (aPlt) were also determined. Seven out of 63 (12.7%) HIV patients were positive for aCL, four of 63 (6.3%) for anti-beta(2)GPI, and five of 63 (7.9%) for aPT. No patients studied were LA positive. Six out of 63 (9.5%) patients were positive for aPlt. One of them showed weak reactivity for GPIb-IX. The platelet count of patients (202+/-63 x 10(3) platelets/microL) was significantly lower than in the controls (343+/-6 x 10(3) platelets/microL) (P<0.001). There was no correlation between the presence of aPL and/or aPlt and thrombocytopenia. Of the HIV-infected patients, 22.2% presented aPL and 9.4% aPlt antibodies. In this study, the presence of aPL and aPlt antibodies was not associated with the development of thrombosis and/or thrombocytopenia.
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PMID:Prevalence of antiphospholipid and antiplatelet antibodies in human immunodeficiency virus (HIV)-infected Chilean patients. 1461 42

Lupus anticoagulants (LA) are immunoglobulins which inhibit phospholipid (PL)-dependent coagulation tests. LA are not specific, as they may reflect the presence of antibodies to human prothrombin, human beta(2)-Glycoprotein I (beta(2)GPI), an association of previous antibodies or other antibodies. Antibodies to human beta(2)GPI act as in vitro anticoagulants by enhancing the binding of beta(2)GPI to PL, and this binding may be influenced by calcium ion concentration. A reduction in final calcium concentration, from 10 mm to 5 mm, increased coagulation times in both dilute Russell Viper Venom Time (dRVVT) and dilute Prothrombin Time (dPT) when plasmas of patients with antibeta(2)GPI antibodies were used. Ten LA patients showed increased dRVVT and dPT ratios from means of 1.5 to 1.7 (P < 0.001) and 2.4 to 4.3 (P = 0.002), respectively. Instead, all LA-positive antibeta(2)GPI antibody-negative patients showed decreased coagulation times from mean ratios of 1.5 to 1.3 (P = 0.004) in dRVVT and from 2.0 to 1.5 (P = 0.01) in dPT. These results are confirmed by running dRVVT of normal plasma spiked with affinity purified IgG antibeta(2)GPI antibodies. Therefore, when a PL-dependent coagulation test is run twice, at different final calcium concentrations, antibeta(2)GPI LA can be identified.
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PMID:A two-step coagulation test to identify antibeta-glycoprotein I lupus anticoagulants. 1509 72

We report on a 32-year old female patient with primary antiphospholipid syndrome (PAPS) and several thromboembolic events despite stable doses of oral anticoagulation, good patient compliance and maintained INR values of >3. Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding occurred while she was anticoagulated. The clinical features appeared to be refractory to oral anticoagulation with phenprocoumon. They were life threatening on each occasion and she developed repetitive episodes of organ damage with cardiac insufficiency (NYHA III), pulmonary hypertension and other residual defects. Even during heparinization recurrent thromboembolism supervened as well as livedo reticularis of the extremities. Lupus anticoagulants (LAC), anticardiolipin (aCL) antibodies and anti-beta(2)-glycoprotein-1 (beta(2)GPI) titers were all markedly elevated. This case report shows that recurrent episodes of thrombosis can occur despite seemingly adequate anticoagulation in patients with CAPS.
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PMID:Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation. 1516 58

The importance of testing for anticardiolipin antibodies (aCL) in the diagnosis of antiphospholipid syndrome (APS) in patients with thrombosis has recently been challenged (ISTH SSC meeting, Boston 2002). We have analyzed the antiphospholipid serology of 123 patients with persistent antiphospholipid antibodies (aPL) attending our hematology department. The cohort was tested for anti-beta(2)-glycoprotein I (beta(2)-GPI) antibodies and aCL of IgG and IgM class and for lupus anticoagulant (LA). Ninety-six of these patients fulfilled Sapporo clinical criteria for APS and 70 of these patients had venous and/or arterial thrombosis. Patients with LA plus anti-beta(2)-GPI antibodies had significantly higher levels of IgG aCL and anti-beta(2)-GPI antibodies than those exhibiting positivity for only LA or anti-beta(2)-GPI antibodies (P < 0.05). Patients with aCL IgG levels over 60 GPLU were found in all cases to be positive for LA and anti-beta(2)-GPI antibodies; 25.2% (31/123) of all patients and 26.04% (25/96) of patients fulfilling Sapporo clinical criteria for APS were positive for aCL only. The mean IgG aCL level in the Sapporo clinical criteria positive patients who had aCL only was 11.5 GPLU (normal < 5 GPLU). These data indicate that omission of aCL testing from the clinical investigation of APS could lead to a failure to diagnose the syndrome in a proportion of patients.
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PMID:The anticardiolipin assay is required for sensitive screening for antiphospholipid antibodies. 1521 88


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