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

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

Snake venom toxins are now regularly used in the coagulation laboratory for assaying haemostatic parameters and as coagulation reagents. Snake venom thrombin-like enzymes (SVTLE) are used for fibrinogen and fibrinogen breakdown product assay as well as detecting dysfibrinogenaemias. Significantly, because SVTLE are not inhibited by heparin, they can be used for defibrinating samples that contain the anticoagulant before assay of haemostatic variables. Prothrombin activators are found in many snake venoms and are used in prothrombin assays, for studying dysprothrombinaemias and preparing meizothrombin and non-enzymic prothrombin. Russell's viper (Daboia russelli) venom (RVV) contains a number of compounds useful in the assay of factors V, VII, X, platelet factor 3 and lupus anticoagulants. Activators from the taipan, Australian brown snake and saw-scaled viper have been used to assay lupus anticoagulants. Protein C and activated protein C resistance can be measured by means of RVV and Protac, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with Botrocetin from Bothrops jararaca venom. Finally, phospholipase A2 enzymes and the disintegrins, a family of Arg-Gly-Asp (RGD)-containing proteins found in snake venoms, show great potential for the study of haemostasis including, notably, platelet glycoprotein receptors GPIIb/IIIa and Ib.
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PMID:Use of snake venom fractions in the coagulation laboratory. 971 87

Antiphospholipid (aPL) syndrome, or APS,--a cluster of conditions that includes arterial or venous thromboses and thrombocytopenia, as well as recurrent fetal loss associated with elevation of aPL antibody--has been reported to occur 2-5 times more frequently in women than men. Strong familial associations lead to the suspicion that aPL positivity, estimated to be present in 2% of the population, is a heritable trait in some cases. Currently, 2 major categories of the illness are recognized--primary and secondary. Secondary APS may be associated with autoimmune disease, malignancy, infectious disease, or drug-induced states. Two assays, one for lupus anticoagulant antibodies and the other for anticardiolipin (aCL) antibodies, are recognized to be the gold standards for serologic diagnosis of the disease. Despite extensive attempts at international standardization of aCL test results, no consensus exists for a value beyond which the test is considered positive. Interestingly, a "dose-effect" relationship for aCL antibody titers has been noted--higher titers of the antibody correlate with increased numbers of thrombotic events. An experimental assay for antibody against beta 2-glycoprotein 1 (beta-2-GP1), a phospholipid-binding protein, may become the most important assay for aPL. Skin findings in APS include livedo reticularis, ulceration, gangrene, or purpura, and, when present, may be the key to diagnosis of this sometimes insidious syndrome. Anticoagulation, usually with warfarin, is the mainstay of therapy, although steroids, immunosuppressive agents, hydroxychloroquine sulfate, and plasmapheresis may all be beneficial adjunctive therapy.
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PMID:Impact of the Antiphospholipid Syndrome: A Critical Coagulation Disorder in Women. 974 73

Cationic germ line gene-encoded anti-DNA antibodies appear to cause inflammatory lesions via deposition and in situ formation of immune complexes, but also perhaps through apoptosis of glomerular mesangial cells. Somatic mutation is not critical for the expression of the electrical net charge of anti-DNA. In one transgenic mouse model, the nephrogenicity of anti-DNA was dependent on the expression of interleukin alpha by epidermal cells. Anti-P autoantibodies are present in the serum of healthy children but are masked by IgG antibodies. Some anti-P antibodies appear to be a subset of antilymphocyte autoantibodies. It was confirmed that anti-Ro/SS-A antibodies react with structurally unrelated conformational epitopes. The combined results of immunofluorescence and enzyme-linked immunosorbent assay in the detection of antineutrophil cytoplasmic antibody has a 99.5% specificity for vasculitis among patients with connective tissue diseases. Antinucleosome antibodies are highly prevalent in patients with systemic lupus erythematosus and show an inverse correlation with nucleosome plasma levels. Transfected T-cell receptor alpha chains specific for nucleosomal autoepitopes from a Th clone that accelerates lupus nephritis, recognized the nucleosomal epitopes presented by antigen presenting cell-bearing 1-A molecules, as well as human DR molecules, via the classical major histocompatibility complex class II groove. IgG antibodies against (beta 2 -glycoprotein (GP)-1 are significantly associated with thrombosis in patients with antiphospholipid syndrome, with a specificity and sensitivity that ranges from 85% to 98% and 32% to 54%, respectively. The lupus anticoagulant activity, or the lack of it, of anti-beta 2-glycoprotein-1 appears to reside on the epitope specificity. Beta 2-glycoprotein-1 binds to apoptotic cells; in turn, anti-beta 2-glycoprotein-1 facilitate apoptotic cell clearance by macrophages. The recently described anti-A2/RA33 autoantibody appears to recognize an epitope capable of distinguishing patients with lupus or with rheumatoid arthritis from those with mixed connective tissue disease.
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PMID:Autoantibodies in systemic lupus erythematosus. 974 55

Antiphospholipid syndrome is characterized by thromboses, fetal losses and antiphospholipid antibodies. This group of antibodies includes lupus anticoagulant, false positive syphilitic reaction, anionic (such as anticardiolipin) and neutral phospholipids antibodies, and anti-phospholipid/cofactors antibodies (such as anti-beta 2-glycoprotein 1). Dominant manifestations are recurrent thrombophlebitis and pulmonary embolism, arterial occlusive disease of young people, obstetrical complications such as fetal losses, livedo, and thrombocytopenia. Warfarin is presently the main treatment.
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PMID:[Antiphospholipid antibodies syndrome]. 978 Nov 33

Beta2-glycoprotein I (beta2GPI) is a cofactor for anti-phospholipid (aPL) binding to cardiolipin (CL)-coated plates. Beta2GPI is also able to bind to endothelial cell (EC) membranes as supported by in-vivo as well as by in-vitro studies. The PL-binding site in the fifth domain of the molecule is involved in the adhesion to endothelium. Actually, specific mutations in this molecular portion abolish endothelium binding and a synthetic peptide spanning the sequence Glu274-Cys288 of the CL-binding site displays comparable adhesion to EC monolayers. Heparan sulphate appears to be one of the anionic EC membrane structures with which cationic beta2GPI interacts, as supported by studies with heparitinase-treated EC. Beta2GPI binding to EC might be related to its activity as endothelial growth factor or as a lipid-carrying glycoprotein. Adhesion of beta2GPI to endothelial membranes offers suitable epitopes for circulating aPL that, once bound, can induce cell activation
Lupus 1998
PMID:Beta2-glycoprotein I as a 'cofactor' for anti-phospholipid reactivity with endothelial cells. 981 72

Two simple procedures were tested for their potential to identify beta2-glycoprotein 1 (beta2GP1) or prothrombin cofactor dependence among lupus anticoagulants (LA). The first comprised mixing test plasma 1:4 with beta2GP1-deficient plasma instead of with normal plasma. beta2GP1 deficiency decreased, but did not abolish most LA detectable in KCT, DRVVT and APTT clotting tests. Mixing 1:4 with bovine plasma was evaluated in a second test based on the KCT in the expectation that prothrombin-dependent LA would be preferentially shortened. Bovine plasma had a similar correcting effect on LA in all three tests considered here. Conversely, a prothrombin antibody was found to have similar prolonging effect on all three of these tests. LA patient plasmas displayed considerable heterogeneity when analysed using a combination of these two tests. The clinical significance of these tests remains uncertain. DRVVT and KCT tests do not appear to discriminate beta2GP1-dependent from prothrombin-dependent LA.
Lupus 1998
PMID:Methods for subtyping lupus anticoagulants. 981 84

The introduction of anticardiolipin antibody (aCL) assay, described in 1983, was able to focus much attention on the study of patients suffering from thrombosis, repeated fetal loss and thrombocytopenia, and allowing the identification of the so called antiphospholipid syndrome (APS). The identification of beta2 glycoprotein I (beta2GPI) as an essential component of the antigenic complex recognized by aCL suggested that this molecule could be a direct target of the antibody response. Since then, different groups have described ELISAs for the detection of anti beta2GPI antibodies, applied to the clinical evaluation of patients with APS, and showing an overall better specificity. Recently, anti beta2GPI were also shown to bind apoptotic bodies resulting in an alteration of their physiological clearance with the triggering of TNFalpha release. This observation suggests that anti beta2GPI may also modify the immunogenicity of apoptotic bodies and of the autoantigens that they contain.
Lupus 1998
PMID:Anti beta2-glycoprotein I antibodies: clinical significance. 981 85

IgA anticardiolipin (IgA aCL) and IgA anti beta2-glycoprotein-I (IgA anti beta2GP1) antibodies are common in SLE and have been associated in some studies with thromboses and thrombocytopenia. Experimental work suggests that IgA aCL are as prothrombotic as the IgG-IgM isotypes. However, in SLE there appears to be less concordance between IgA aCL and IgA anti beta2GP1 as compared with the concordance between IgG and IgM isotypes, suggesting significant differences in their origins and specificities. For example, there may be a greater mucosal contribution to production of IgA antibeta2GP1 than IgA aCL. Infections may have a greater role in the presence of IgA aCL than IgA antibeta2GP1 antibodies.
Lupus 1998
PMID:Significance of IgA antiphospholipid antibodies. 981 86

The presence of antiphospholipid (aPL) antibodies has been associated with thrombosis, pregnancy loss and thrombocytopenia in the antiphospholipid syndrome (APS). The anticardiolipin and the lupus anticoagulant tests are frequently used to detect aPL antibodies. The anticardiolipin ELISA utilizes cardiolipin coated on polystyrene plates as antigen and is a very sensitive test but lacks specificity, since it can be positive in a number of infectious (such as syphilis, HIV) and autoimmune diseases other than APS. In an effort to improve specificity, new ELISA techniques that employ alternative antigens (such as beta2-glycoprotein 1, particularly when coated onto oxidized microtiter plates or mixture of phospholipids) have been developed. Several investigators have reported that these new assays enable more specific determination of aPL antibodies and thus can be used more reliably for the diagnosis and confirmation of APS. This article examines the results of those studies, including data that shows correlations of these assays with clinical manifestations of APS, and proposes a new protocol for the use of laboratory tests in the diagnosis of APS.
Lupus 1998
PMID:Diagnosis of the antiphospholipid syndrome: a proposal for use of laboratory tests. 981 93


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