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)

Thrombocytopenia in patients with acute systemic lupus erythematosus (SLE) frequently presents the clinician with considerable diagnostic and therapeutic difficulties. In this Grand Round, we present a 48-yr-old woman with a 7 yr history of lupus, who presented with acute proliferative glomerulonephritis and nephrotic syndrome, pneumonia, profound hypocomplementaemia and a severe microangiopathic haemolytic anaemia with associated thrombocytopenia. Her thrombocytopenia proved initially refractory to conventional immunosuppressive therapy, and corticosteroids, and resolved only with plasma exchange and repeated fresh frozen plasma infusions. Serological testing revealed high-titre antinuclear antibodies (ANA) and markedly raised antibodies to double-stranded (ds) DNA, but no significant elevation in anticardiolipin antibodies. Platelet-associated IgG and IgM and antibodies to the CD36 glycoprotein antigen, expressed on platelets and endothelium, were detected in the serum. We address some of the difficult diagnostic and management issues raised by this complex patient and the possible immunopathological links between antibodies to CD36, immune-mediated red cell destruction, thrombocytopenia and thrombotic microangiopathic haemolytic anaemia.
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PMID:Systemic lupus erythematosus, thrombocytopenia, microangiopathic haemolytic anaemia and anti-CD36 antibodies. 925 16

Male (NZW x BXSB)F1 (W/BF1) mice develop a systemic lupus-like syndrome characterized by thrombocytopenia, coronary vascular disease, nephritis, and anticardiolipin antibodies. Three stable hybridoma cell lines secreting monoclonal anticardiolipin antibodies were developed from these mice by fusing their splenic lymphocytes with nonsecreting myeloma cell line, NS-1. Monoclonal antibody A1.17 reacted with cardiolipin in a beta2-Glycoprotein I-dependent manner. The epitope for this antibody consisted of beta2-glycoprotein I bound to cardiolipin or immobilized on plastic plates. Other anionic phospholipid-binding proteins, such as prothrombin or annexin V, had no significant effect in the reactivity of these antibodies. The specificity is similar to the autoimmune anticardiolipin antibodies described in patients with systemic lupus erythematosus and other infectious diseases. In contrast, monoclonal antibodies A1.72 and A1.84 reacted with cardiolipin in the absence of beta2-glycoprotein I. Beta2-glycoprotein I, either in the fluid phase or bound to cardiolipin, inhibited the binding of these antibodies. The specificity of the latter two antibodies was similar to that described in patients with syphilis and allied disorders. Both types of antibodies had lupus anticoagulant properties. Thus lupus-prone male (NZW x BXSB)F1 (W/BF1) mice develop both beta2-glycoprotein I-dependent and beta2-glycoprotein I-independent anticardiolipin antibodies.
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PMID:Characterization of beta2-glycoprotein I-dependent and -independent "antiphospholipid" antibodies from lupus-prone NZW/BXSB F1 hybrid male mice. 932 49

Snake venom toxins have an established role in the coagulation laboratory for the assay of haemostatic parameters and a potential role for therapeutic treatment of thrombotic disorders. In the laboratory, snake venom thrombin-like enzymes (SVTLEs) are used for the assay of fibrinogen and detection of fibrinogen breakdown products and dysfibrinogenaemias. Importantly, because SVTLEs are not inhibited by heparin, they can be used for assaying antithrombin III and other parameters in samples which contain heparin. Prothrombin activators occur in many snake venoms and these have become established in the assay of prothrombin, in the study of dysprothrombinaemias and in the preparation of meizothrombin and non enzymic forms of prothrombin. Russell's viper (Daboia russelli) venom contains a number of useful compounds including toxins which can be used to assay blood clotting factors V, VII, X, platelet factor 3 and lupus anticoagulants (LA). More recently, activators from the taipan, Australian brown snake and saw-scaled viper have been used to assay LA. Proteins C and S can be measured by means of protac, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with botrocetin from Bothrops jararaca venom. The disintegrins, a large family of Arg-Gly-Asp (RGD)-containing proteins found in snake venoms, show great potential for the study of platelet glycoprotein receptors, notably, GPIIb/IIIa and Ib, and in the treatment of arterial thrombotic disease. Established SVTLEs used in clinical practice include ancrod and defibrase although success with these agents has been limited. A further group of enzymes under consideration as thrombolytic agents are the fibrinogenases.
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PMID:Practical applications of snake venom toxins in haemostasis. 942 23

Antiphospholipid antibodies are a family of autoantibodies including lupus anticoagulant and anticardiolipin antibodies that appear to react with negatively charged phospholipids. These antibodies induce thrombosis and pregnancy complications including recurrent stillbirth, recurrent miscarriage, pre-eclampsia and intra-uterine growth retardation. Recent evidence indicates that antiphospholipid antibodies do not bind directly to phospholipid but rather to phospholipid-binding proteins or to a combination of phospholipid and phospholipid-binding proteins. This opens the possibility that antiphospholipid antibodies may be pathogenic by disrupting the function of phospholipid-binding proteins rather than membrane phospholipid. The antigenic role of one phospholipid-binding protein, beta 2 glycoprotein, has been studied in the greatest detail and is reviewed. Despite being highly conserved and expressed at high levels, the physiological function of beta 2 glycoprotein 1 remains unknown. However, a number of putative roles have been proposed which allow speculation as to the mechanism by which antiphospholipid antibodies may disrupt haemostasis and pregnancy.
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PMID:Antiphospholipid antibodies or not? The role of beta 2 glycoprotein 1 in autoantibody-mediated pregnancy loss. 943 Jul 43

Platelet activation may contribute to the increased risk of thrombotic complications in patients with antiphospholipid antibodies (aPL). The increased urinary excretion of 11-dehydro-thromboxane B2 (11-DH-TXB2) reported in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (aCL) reflects in vivo platelet activation. However the majority of autoimmune aPL are directed to beta2 glycoprotein I (beta2GPI) or prothrombin (II). We investigated the relationship of these antibodies with 11-DH-TXB2 urinary excretion in 34 patients with aPL. The urinary 11-DH-TXB2 was measured by EIA after extraction on octadecyl columns and purification on silica gel columns, which was validated by thin-layer chromatography/EIA procedure. A significantly increased excretion of 11-DH-TXB2 was found in aPL patients as compared to 18 normal controls (p <0.01). But no differences were seen in the excretion of 11-DH-TXB2 between patients with or without LA, or aCL. The number of patients with anti-II antibodies was too small to draw any conclusion. In contrast, patients with anti-beta2GPI antibodies IgG at moderate/high titre (group A, n = 14) had higher levels of urinary 11-DH-TXB2 than those at low titre or negative (group B, n = 20) (p = 0.01). The group A of patients presented an increase in 11-DH-TXB2 compared to controls (p <0.001), but no statistically significant difference was found between patients from the group B and normal controls. A correlation between levels of urinary 11-DH-TXB2 and titre of antibodies was only found for anti-beta2GPI-IgG (r(s) = 0.51, p <0.005). Our data show that the observed platelet activation in aPL patients is related to the presence of antibodies reacting with beta2GPI.
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PMID:Anti-beta2 glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: association with increased excretion of platelet-derived thromboxane urinary metabolites. 945 20

Clusterin, a widely distributed glycoprotein, is detected in most tissues and in numerous physiological fluids. In the kidney, this protein is constitutively expressed in tubular epithelial cells, and its expression is enhanced following tubular injuries. In addition, clusterin has been detected in glomerular immune deposits of glomerulonephritis. The present study was designed to define the sites of clusterin mRNA accumulation in murine lupus-like nephritis in comparison with murine tubulopathies. In lupus-like nephritis, a significant increase of clusterin mRNA abundance was demonstrated. This up-regulation was localized exclusively in tubular epithelial cells exhibiting tubulointerstitial alterations, whereas no clusterin mRNA was detectable in diseased glomeruli, excluding an active synthesis of clusterin by glomerular cells. A similar tubular increase of clusterin mRNA abundance was observed in myeloma-like cast nephropathy induced by IgG3 monoclonal cryoglobulins and even in the absence of any detectable histological alterations in a model of septic shock induced by the injection of bacterial lipopolysaccharides. Our results suggest that tubular epithelial cells are the only sites of clusterin mRNA accumulation during the course of lupus-like nephritis and that the tubular up-regulation of clusterin gene expression may reflect the cellular response to various types of tubular injuries.
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PMID:Tubular up-regulation of clusterin mRNA in murine lupus-like nephritis. 954 56

Antibodies to beta 2-glycoprotein in the serum of patients with antiphospholipid syndrome (APS) were found by many investigators, but their results appeared contraversional. We studied clinical significance of antibodies to beta 2-glycoprotein I (anti-beta 2-GPI) in patients with SLE. 69 patients with verified SLE were examined for lupus anticoagulant (LA), antibodies to cardiolipin (aCL) and anti-beta 2-GPI. 44(65%), 46(67%), 49(71%), 19(28%), 16(23%) patients were positive for LA, IgG-aCL, IgM-aCL, IgG-anti-beta 2-GPI and IgM-anti-beta 2-GPI, respectively. Hyperproduction of IgG-anti-beta 2-GPI correlated with APS development as a whole, its separate clinical symptoms (venous and arterial thromboembolism, obstetric pathology and thrombocytopenia) and some comcomitant clinical signs (trophic crural ulcer, hemolytic anemia, valvular heart disorders). Moreover, an increase in concentration of IgM-anti-beta 2-GPI was associated with habitual abortion. Both isotypes of anti-beta 2-GPI occurred more frequently in the sera positive by LA and aCL. It is interesting that we discovered IgG-anti-beta 2-GPI more often in early than late postthrombolytic period. Thus, anti-2b2-GPI is a new serological marker of APS. Its detection is clinically important for upgrading diagnosis of APS.
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PMID:[Antibodies to beta2-glycoprotein I in systemic lupus erythematosus: new laboratory marker of antiphospholipid syndrome]. 957 46

Fifteen years have passed since Hughes reported the detailed clinical description of antiphospholipid syndrome (APS), and it is now recognised as one of the most common prothrombotic disorders. Its main clinical features are recurrent thrombosis (both venous and arterial), recurrent pregnancy loss and thrombocytopenia associated with the presence of antiphospholipid antibodies (aPLs). aPLs are a heterogeneous group of autoantibodies detected by either clotting or immunological assays. They include lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and antibodies against other phospholipids (PLs). Recently the aPLs family has expanded to include antibodies whose specificity are claimed to be directed not only towards PLs, but also towards plasma proteins and their complex with PLs. Animal models are providing important new data on clinical and pathogenic aspects of APS. The detection of antibodies against beta 2 glycoprotein I by a simple and rapid enzyme-linked immunosorbent assay (ELISA) may facilitate the recognition of "pathogenic" aCL in APS. Regarding the treatment of APS, long-term anticoagulation therapy is needed to prevent recurrences.
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PMID:Advances in antiphospholipid (Hughes') syndrome. 958 77

Antiphospholipid antibodies were first linked to pregnancy loss more than 20 years ago, and the condition known as antiphospholipid syndrome is perhaps the most convincing 'immunologic' disturbance other than anti-erythrocyte and anti-platelet alloimmunization disorders. Specific criteria for the antiphospholipid syndrome have been delineated, the anticardiolipin assay has been standardized, and authorities agree on laboratory criteria defining lupus anticoagulant. Nonetheless, considerable confusion exists regarding antiphospholipid syndrome and related reproductive problems. The state of affairs primarily derives from two problems: the first is the premature introduction of non-standardized antiphospholipid assays into clinical use without rigorous standardization and prior to convincing proof of clinical utility. As a result, well-intending, but less well-versed clinicians sometimes make the diagnosis of antiphospholipid syndrome in women who are negative for lupus anticoagulant and anticardiolipin antibodies. This is especially confusing in the face of of growing evidence that the relevant in vivo antiphospholipid antigen is formed by a complex between beta 2-glycoprotein 1 and phospholipids. A second major problem is that of unwarranted discrepancies in the clinical and laboratory features of patients considered to have a diagnosis of antiphospholipid syndrome. This problem is most apparent in the case selection for pregnancy-loss treatment series and trials. Many series have included women with predominantly pre-embryonic and embryonic pregnancy losses, while others included a large majority of patients with one or more second or third trimester pregnancy losses. Some treatment trials purposefully excluded patients with a history of thrombosis or systemic lupus erythematosus, features found in nearly 50% of patients in other series. Though most authorities require the presence of either lupus anticoagulant or medium-to-high titer IgG anticardiolipin antibodies to make a diagnosis of antiphospholipid syndrome, in some series no more than half of the study patients had lupus anticoagulant and as many as 20% had only IgM anticardiolipin antibodies. It is very unlikely that patients with such disparate clinical and laboratory findings have the same autoimmune syndrome, and a stated or implicit diagnosis of antiphospholipid syndrome in such a wide variety of women is scientifically unsound and clinically dangerous. The relationship between antiphospholipid antibodies and poor reproductive outcomes must be approached through rigorous scientific study and appropriate treatments established by well-designed clinical trials.
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PMID:Antiphospholipid antibodies and reproductive outcome: the current state of affairs. 961 79

The antiphospholipid antibodies (aPL) present in "antiphospholipid-protein syndrome and autoimmune disorders" are associated with thromboembolic episodes, such as venous and/or arterial thrombosis and fetal loss. Patients with antiphospholipid antibodies have, by definition, laboratory abnormalities in either coagulation assays or various solid phase immunoassays ELISA or radioimmunoassays (RIA). These assay systems were initially thought to detect antibodies against phospholipids. The problem was complicated when it was reported that phospholipid is not the sole antigen but only a part of it, the other contribution being due to b2-glycoprotein I (b2-GP I). More findings, demonstrate that the aPL are in fact anti-b2-GP I antibodies directed against a epitope which is expressed when b2-GP I is bound to anionic phospholipid or another suitable surface. Recent studies have demonstrated that antibodies related to lupus anticoagulant (LA) induce an anticoagulant activity in b2-GP I. Some of these LA require binding to phospholipid. However, not all LA require b2-GP I as a cofactor. Human prothrombin is an antigen for some LA IgG's. Finally, a subclassification of phospholipid-dependent coagulation test anticoagulants is described, there appear to be several subclasses of LA, and the clinical and laboratory criteria required to establish the diagnosis of antiphospholipid-protein syndrome is emphasised.
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PMID:[Lupus anticoagulants versus antiphospholipid antibodies]. 964 46


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