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)

Anti-cardiolipin antibody (aCL) in SLE patients reacts with cardiolipin/beta 2-GP1 complex. In order to disclose clinical significance of aCL in patients with SLE, aCL was determined by newly-developed anti-CL.beta 2-GP1 kit [Yamasa] EIA in 58 patients with SLE and the relationship between clinical manifestation of SLE and the presence of aCL was examined. Anti-cardiolipin antibody was positive in 20 patients (34.5%). In 20 SLE patients with positive aCL, livedo reticularis in 7, retinal vein thrombosis in 3, thrombophlebitis in 3 and other vasculo-occlusive episodes were observed as a characteristic clinical features of positive aCL. In contrast, a SLE patient complicated by ileal perforation due to necrotizing angiitis had negative aCL. Other clinical and laboratory features associated with aCL include recurrent fetal loss and thrombocytopenia.
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PMID:[Clinical significance of anti-cardiolipin antibody in patients with systemic lupus erythematosus (SLE)]. 786 86

Lupus anticoagulants, commonly found in the immunoglobulin fraction of patients with the antiphospholipid syndrome (APS), and the normal plasma protein beta 2-glycoprotein 1 (beta 2GP1) may both contribute to the in vitro impairment of prothrombin activation associated with the APS. We examined the effects upon prothrombin activation supported by phospholipid vesicles of plasma IgG preparations from APS patients in the presence and absence of beta 2GP1. Using a purified system for measurement of prothrombin activation to thrombin, we demonstrated significant phospholipid concentration-dependent inhibition of prothrombin activation in the absence of beta 2GP1 by 11 consecutive patient IgG preparations. The degree of inhibition of prothrombin activation by equivalent concentrations of patient IgG correlated well with the extent of prolongation of the plasma clotting time in lupus anticoagulant assays of whole patient plasma. Additional studies with eight patient IgG preparations indicated that the addition of beta 2GP1 to patient IgG-phospholipid vesicle mixtures resulted in either independently additive inhibition by the two protein species (six cases) or potential inhibition of beta 2GP1 of the IgG inhibitory activity demonstrable in the absence of beta 2 GP1 (two cases). In addition, beta 2GP1-independent inhibition of prothrombin activation also occurred with three patient IgG preparations obtained by affinity binding to cardiolipin.
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PMID:Inhibition of prothrombin activation by antiphospholipid antibodies and beta 2-glycoprotein 1. 799 95

Clinical analysis was performed on anti-cardiolipin x beta2 glycoprotein 1 (ACL x beta2 GP1) antibody positive patients with collagen vascular diseases. Nine patients out of 89 showed positive aCL x beta2 GP1 antibody which was a relatively lower percentage compared to that of othoffanti-phospholipid antibodies, such as anti-cardiolipin antibody (23 out of 58), lupus anti-coagulant (15 out of 51) or biological false positive (BFP) test for syphilis (10 out of 50). However, 8 patients out of 9 with positive aCL x beta2 GP1 antibody showed thrombotic lesions, a relatively higher frequency compared to that seen in aCL x beta2 GP1 negative patients. Among these cutaneous manifestations, livedo reticularis and palmar nodules with histopathological evidence of thrombosis were the most characteristic features. All but one patient with palmar nodules showed positive aCL x beta2 GP1 antibody, anti-cardiolipin antibody and lupus anticoagulant.
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PMID:Clinical analysis of anti-cardiolipin.beta 2 glycoprotein 1 antibody positive patients in anti-phospholipid syndrome. 866 20

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

Utilizing this unique animal model of thrombosis we demonstrated that human (IgG, IgM or IgA) polyclonal and monoclonal antiphospholipid antibodies derived from APS patients have a significant enhancing effect on thrombus formation. This effect is reversed by treatment of the mice with hydroxychloroquine (plaquenil). In addition murine polyclonal and monoclonal anticardiolipin antibodies induced by active immunization with human beta 2-GP1 or human anticardiolipin antibodies showed to have thrombogenic properties in CD1 mice. Antibodies with antihuman beta 2-GP1 activity alone did not seem to affect thrombus formation.
Lupus 1996 Oct
PMID:In vivo models of thrombosis for the antiphospholipid syndrome. 890 80

In examining reasons for premature atherosclerosis in systemic lupus erythematosus (SLE), we previously reported low levels of the cholesterol transport protein apolipoprotein A1 (apoA1) in these patients, and specific antibodies to purified apoA1 were identified in the sera of 5 out of 30 lupus patients. The current study was initiated to determine whether these antibodies are common in lupus patients. 520 serum samples from 175 patients with SLE or primary antiphospholipid syndrome (PAPS) were tested for antibodies to purified apoA1. Positive sera were retested for binding to apolipoprotein incorporated into reconstructed nascent or mature high-density lipoprotein (HDL). Autoantibodies to apoA1 were found in 32.5% of patients with SLE and 22.9% of patients with PAPS, associated with the presence of aPL (anti-beta2 glycoprotein-1, anti-beta2 GP1) antibodies. When reconstructed, nascent and mature HDL molecules were compared as antigen-containing environments, positive sera reacted best to apoA1 embedded in mature HDL molecules. This report confirms the high prevalence of antibodies to apoA1 in patients with systemic lupus and suggests a high affinity of these antibodies for mature HDL.
Lupus 1998
PMID:Frequency of antibodies to the cholesterol transport protein apolipoprotein A1 in patients with SLE. 969 40

We describe the isolation and identification of three components required for the Rubino reaction (RR), which is the rapid sedimentation of formalinized sheep red-blood cells (SRBC) initiated by serum from leprosy patients with defective Mycobacterium leprae-specific cell immunity. The Rubino reaction factor (RRF) required for this phenomenon, previously identified as an immunoglobulin M (IgM), was purified from leprosy patient serum by adsorption to formalinized SRBC. Purified RRF IgM, when added to formalinized SRBC, did not produce a positive RR. However, when the contact was carried out in the presence of normal human serum (NHS), cells rapidly sedimented. The purified cofactor from NHS contained two components of 70 000 and 50 000 molecular weight (MW), as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The latter was recognized by the RRF IgM on immunoblot and its N-terminal sequence indicated that it was beta2-glycoprotein 1 (beta2-GP1), an anionic phospholipid-binding protein. Methanol-treated formalinized SRBC did not support the RR. Thin-layer chromatography of an extract of membranes indicated that the SRBC ligand was a cell-surface phospholipid. Cardiolipin inhibited the RR. These data demonstrate that the RR involves a trimolecular interaction in which IgM, beta2-GP1 and an SRBC phospholipid participate. By analogy with the antiphospholipid antibodies (anti-PL) that occur in autoimmune processes, serum samples from 29 systemic lupus erythematosus patients with high levels of anticardiolipin antibodies were submitted to the RR. A positive RR was obtained for 45% (13 of 29 patients). These results modify the paradigm of the absolute specificity of the RR for leprosy and demonstrate that RRF IgM is a beta2-GP1-dependent anti-PL.
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PMID:The Rubino test for leprosy is a beta2-glycoprotein 1-dependent antiphospholipid reaction. 1101 66

The term "antiphospholipids" (aPLs) refers to an heterogeneous family of antibodies diagnosed either by clotting tests: the lupus anticoagulants or by Elisa: anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-beta2GP1) especially. aPLS recognize phospholipids, alone or bound to plasma protein cofactor(s), or the cofactors themselves. aPLs have long been described in autoimmune diseases such as SLE, but may also be found in other clinical settings including infections, malignancies and drug administration. Their persistent presence can be associated with venous and/or arterial thrombotic complications and/or recurrent miscarriage, thus defining the "antiphospholipid syndrome" (APS). The heterogeneity of aPLs makes a comprehensive approach to laboratory investigation essential. Detection of lupus anticoagulants relies on increased clotting times in phospholipid-dependent tests. Their 4 step diagnosis includes: 1) screening (by at least two different tests); 2) demonstration of an inhibitory activity; 3) evidence of its phospholipid dependence; 4) exclusion of an associated coagulopathy. Among the aPLs detected by Elisa, IgG aCL are the most frequently investigated. However, other antibodies may represent useful biological tools. Among them, anti-beta2GP1 are thought to be more closely associated with a history of thrombosis than aCL and testing for anti-beta2 GP1 should now be systematically included in the biological diagnosis of APS. The Elisa used for aCL and anti-beta2GP1 are not fully standardized, and a number of methodological parameters may account for the interlaboratory discrepancies often observed. The clinical importance of other antibodies such as antiphosphatidylethanolamine, antiprothrombin or antiannexin V is being evaluated. An appropriate laboratory investigation of APS should, in all cases, combine the use of clotting and immunological assays, and assess the persistence of autoantibodies over time.
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PMID:[Antiphospholipid antibodies: clinical significance and biological diagnosis]. 1102 99

The possibility of a genetic predisposition to develop the antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies and lupus anticoagulant has been addressed by family studies and by population studies. Various studies suggest a familial occurrence of anticardiolipin antibodies and lupus anticoagulant, with or without clinical evidence of APS. This familial tendency could be genetically determined. Multiple human leukocyte antigen-DR or -DQ associations with antiphospholipid antibodies have been described. Genetic studies of beta(2)-glycoprotein-1(GP1) polymorphisms have been determined and valine/leucine polymorphism could be a genetic risk for having anti-beta(2)-GP1 antibodies and APS. Compared with polymorphism of beta(2)-GP1 as a genetic risk factor for APS, beta(2)-GP1 deficiency is not associated with thrombosis and patients with APS usually have normal or somewhat elevated levels of beta(2)-GP1. The antigen specificity of antiphospholipid antibodies and the pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial.
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PMID:Antiphospholipid syndrome: genetic review. 1296 26

Forty-five patients with systemic lupus erythematosus (SLE) were investigated to evaluate the role of antiphospholipid antibodies in causation of thrombosis in Indians. The antiphospholipid antibodies studied included lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-beta(2)-glycoprotein 1 (a beta(2)-GP1). Twenty-seven patients (60%) had clinical manifestations of antiphospholipid antibody syndrome. Nineteen patients (42.2%) had a history of thrombosis, and eight (17.7%) had a history of recurrent fetal loss. aBeta(2)-GP1 was (IgG) was positive in 23 (51.1%), aCL in 13 (28.8%), and LAC in four (8.8%). Of 19 patients with thrombosis, 14 (73.6%) were positive for abeta(2)-GP1, eight (42.1%) for aCL, and none of them was positive for LAC. Of the eight patients with recurrent fetal loss, two (25%) patients were positive for beta(2)-GP1, five (62.5%) for aCL, and one (12.5%) for LAC. Of 18 patients without any manifestations of antiphospholipid syndrome (APS), seven patients (38.8%) were positive for abeta(2)-GP1, and three (16.6%) for aCL and LAC each. It is concluded that presence of abeta(2)-GP1 increases the risk of thrombosis and therefore should be looked for in all cases of SLE to consider prophylactic antithrombotic therapy in these patients.
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PMID:Beta2 glycoprotein 1 in Indian patients with SLE. 1582 30


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