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 platelet function was studied in 23 patients with systemic lupus erythematosus, all of whom met the diagnostic creteria established by the American Rheumatism Association. They were not under any treatment, especially with any drug that might interfere with platelet function. The same study was performed on a control group composed of volunteers donors at a blood bank. The platelet count was definitely lower in the patients with lupus than in the control subjects (p less than 0.0005), although a clear thrombopenia was observed in only two indivduals (8.7 percent). Anti-platelet antibodies were found in only six cases (26 percent). There was a linear correlation between thrombopenia and the presence of hemorrhagic diathesis and low levels of C4 and CH50 components. Plateler adhesiveness was clearly lower in the lupus group than in the control group (p less than 0.0005). The presence of kidney disease determined a greater impairment of the platelet adhesiveness (p less than 0.0025). A notable defect on platelet aggregation was induced by ADP, adrenaline and collagen. This was more apparent in the group of patients exhibiting a higher degree of clinical activity and in those who showed a serum complement decrease. The mechanism responsible for this thrombopathy appears to be an interference in the platelet function due to the presence of circulating immunocomplexes. They adhere to the platelet membrane blocking its function and inhibiting the release of the necessary thrombocytic components for the second phase of the aggregation. This platelet alteration is not usually manifested clinically; for this reason no relationship was found between this platelet defect and the presence of hemorrhagic symptoms in our patients. The condition is reversible and may disappear after therapy with steroids and/or immunosuppresive agents.
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PMID:[Platelet function in systemic lupus erythematosus (author's transl)]. 45 1

A lupus-type anticoagulant which causes strong inhibition of the partial thromboplastin time with kaolin (PTTK), the stypven time, and the thrombin generation tests has been investigated. All tests for platelet function were normal, as were all specific coagulation factor assays with the exception of a slightly reduced factor XI in this patient. A diethylaminoethyl-cellulose-immunoglobulin (DEAE-cellulose-IgG) fractionation of the patient's plasma produced two peaks containing inhibitory activity in the PTTK test. The first of these peaks had a cloudy appearance, suggesting the presence of immunoglobulin aggregates. Studies with IgG aggregates prepared from normal IgG and from the patient's IgG demonstrated that such aggregates were not the cause of inhibition. It was possible to neutralize the inhibitory activity of the purified IgG but not platelet-poor plasma (PPP) with a rabbit anti-IgG. The inhibition of the patient's PPP in the thrombin generation, the contact product, and the stypven time tests were corrected by the inclusion in the test system of platelets activated either by aggregation due to adenosine diphosphate (ADP) or formalin fixation and washing. These studies lend support to earlier findings that platelets interact at several sites in the coagulation cascade.
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PMID:Demonstration of a platelet bypass mechanism in the clotting system using an acquired anticoagulant. 73 36

Hematological complications seen in systemic lupus erythematosus (SLE) patients may be caused by the binding of specific autoantibodies to platelets, but the epitopes on platelets responsible for antibody binding and the mechanisms by which autoantibodies induce hemostatic abnormalities in SLE patients remain unknown. We have previously demonstrated that polyspecific platelet-binding antibodies can be derived from SLE patients. In the present study, we have characterized an SLE-derived polyspecific hybridoma antibody, 9604, which was previously shown to be strongly cytotoxic to platelets in vitro and to have weak lupus anticoagulant activity. We demonstrated that this antibody does not bind to fixed intact platelets in an enzyme-linked immunoassay (ELISA), but does react with lysed, washed or ADP-activated platelets. By Western blotting analysis, antibody 9604 was unique among other platelet-binding autoantibodies in that it reacted mainly with polypeptides of approximately 200,000 and 32,000 molecular weight (MW) in platelets. In blots of endothelial cell proteins, 9604 reacted with a band of approximately 200,000 MW, but no 32,000 MW reactive band was observed. Based on these findings, we postulate that antibody 9604 may bind to a protein or proteins of 32,000 MW exposed on the platelet surface during activation. To our knowledge, this is the first demonstration of a human hybridoma monoclonal antibody derived from an SLE patient which distinguishes between activated and resting platelets. Further characterization of the proteins recognized by this autoantibody may provide insight into the mechanisms responsible for the production and pathogenesis of anti-platelet autoantibodies in patients with SLE.
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PMID:A systemic lupus erythematosus-derived human hybridoma autoantibody reactive with antigens expressed on ADP-activated platelets. 191 Apr 24

To clarify the pathogenesis of antiphospholipid antibody (aPL) syndrome, the reactivities of anticardiolipin antibodies (aCL) in sera of patients with systemic lupus erythematosus (SLE) or other diseases to fresh, activated or destroyed blood cells were examined by the inhibition assay using an enzyme-linked immunosorbent assay. In addition, the effects of lupus anticoagulants (LA) in the patients' plasma and of immune complexes formed between LA and PL antigens on platelet aggregations were also determined. The IgG-aCL activity of patients' sera was markedly inhibited by pre-incubation with freeze-thawed blood cells, including erythrocytes (RBC), mononuclear cells (MNC) and platelets, but not fresh platelets or RBC. The aCL activity was slightly inhibited by fresh MNC, and was definitely inhibited by thrombin-activated platelets and polymorphonuclear cells (PMN) stimulated with phorbol 12-myristate 13-acetate (PMA). However, the activity was not inhibited by platelets stimulated with adenosine 5'-diphosphate (ADP; 10 microM). Twenty-two LA positive plasma and 17 LA negative plasma from patients similarly enhanced the aggregation of platelets which were obtained from healthy adults and stimulated with low concentrations of ADP (1 or 2 microM). However, such enhancement of platelet aggregation was not observed when high concentrations of ADP (5 microM) or collagen (2 micrograms/ml) were used as stimulators. In four of the 16 LA positive plasma examined, the mixture of plasma and phospholipid reagent for activated partial thromboplastin time induced platelet aggregations without the other stimulations, but the plasmas themselves did not induce such a reaction. The above results indicate that the aPL from patients do not react with intact blood cells in vitro, but they can react with activated or destroyed blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivities of antiphospholipid antibodies to blood cells and their effects on platelet aggregations in vitro. 212 28

A patient with microvascular thrombosis and thrombocytopenia was found to have a high-titre lupus anticoagulant. The biological effects of the patient's lupus anticoagulant were studied using whole patient serum and plasma. Staph Protein A eluate, and affinity-purified lupus anticoagulant. The latter was isolated by immunoadsorption of serum onto cardiolipin/phosphatidylserine/cholesterol liposomes. Each source of lupus anticoagulant demonstrated 'anticoagulant' activity, defined as prolongation of a modified kaolin clotting time, and contained antibody which bound to endothelial monolayers. Each interfered with thrombin-mediated prostacyclin release from endothelial cells, but had no effect on arachidonate-induced prostacyclin release. In addition, the lupus anticoagulant selectively blocked platelet aggregation in response to thrombin, but not in response to arachidonate, ADP or epinephrine. Lupus anticoagulant also reduced thrombin-stimulated shifts in cytosolic calcium. Thrombin-mediated membrane inositol metabolism and total thrombin binding to endothelium were unaffected by lupus anticoagulant, and another endothelial anticoagulant function related thrombin binding. Protein C activation by thrombomodulin, was not altered. We conclude that the binding of lupus anticoagulant to endothelial cells and platelets does not prevent all thrombin signalling events, but does interrupt prostacyclin production.
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PMID:Lupus anticoagulant induces a selective defect in thrombin-mediated endothelial prostacyclin release and platelet aggregation. 249 19

The neonatal lupus syndrome is the most common cause of isolated congenital heart block. There is, at present, little information about the putative role of anti-SS-A/Ro SS-B/La antibodies in the pathogenesis of congenital heart block in the neonatal lupus syndrome. Using an in vitro experimental model, the present study was designed to test the hypothesis that IgG antibodies in the sera of anti-SS-A/Ro SS-B/La-positive mothers of infants with isolated congenital heart block bind to and affect the transmembrane action potential of rabbit cardiac tissue. The results demonstrate a preferential inhibition of membrane repolarization (ADP-50 and ADP-90) and staining of cardiac cells within the neonatal, in contrast to the adult, rabbit heart by sera and IgG-enriched fractions from anti-SS-A/Ro SS-B/La-positive individuals. The results of the electrophysiologic studies demonstrate a pathophysiologic role for the IgG fraction of anti-SS-A/Ro SS-B/La-positive maternal sera in inhibiting neonatal rabbit cardiac repolarization. It is possible that antibodies to similar determinants expressed on the cell membrane of cardiac-conducting cells also may play a pathophysiologic role in the development of idiopathic congenital heart block in humans.
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PMID:Anti-SS-A/Ro SS-B/La antibodies bind to neonatal rabbit cardiac cells and preferentially inhibit in vitro cardiac repolarization. 278 47

Certain drugs are a frequent source of antinuclear antibody (ANA) induction, and ANA is invariably present in the few patients who progress to the drug induced lupus syndrome. This report concerns the fine specificity of the ANA response to hydralazine, penicillamine, and sulphasalazine therapy. Using highly purified individual histones in fluorimetric assays, antihistone antibodies are always detectable, often in large amounts, but the pattern of response to individual histones is variable and not drug specific. In addition to the response to the three histones H1, H2B, and H3 reminiscent of idiopathic systemic lupus erythematosus, antibody to histone H2A predominates in some drug induced cases. Contrary to previous thought, histones are not the sole target of the antinuclear response: we also demonstrate a significant correlation between ANA titre and antibody to poly(adenosine diphosphate-ribose). Like the histones, this is a macromolecule that can bind to deoxyribonucleic acid (DNA). It is proposed that drug induced damage to chromatin leads to ANA production, while drug induced impairment of complement activity may then enable these autoantibodies to mediate the lupus syndrome.
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PMID:Antibodies to the five histones and poly(adenosine diphosphate-ribose) in drug induced lupus: implications for pathogenesis. 288 34

10 consecutive patients fulfilled the diagnostic criteria for lupus anticoagulant. 4 had concomitant systemic lupus erythematosus, 1 Waldenstrom's disease and 5 had no apparent underlying disease. Only the case with Waldenstrom's disease presented a bleeding tendency, with bleeding time greater than 20 min; the others had a history of thrombotic complications. A defect of platelet aggregation induced by ADP, epinephrine, collagen and arachidonic acid was documented in the Waldenstrom's disease case whose lupus anticoagulant was an IgM. In the others, lupus anticoagulant, identified as IgG immunoglobulins, produced no aggregation abnormalities. However, beta-thromboglobulin levels in platelets, plasma and urine were consistent with a pattern of platelet activation in all cases. IgG immunoglobulins separated from sera of 6 patients showed lupus anticoagulant activity, with no effects on platelet aggregation of normal platelet-rich plasma, but they induced secretion of beta-thromboglobulin from normal platelets.
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PMID:Interaction between platelets and lupus anticoagulant. 296 26

The platelet binding properties of human monoclonal lupus autoantibodies have been studied. These IgM autoantibodies, produced by human X human hybridomas derived from lymphocytes of patients with systemic lupus erythematosus, are known to bind to single-stranded DNA. Four anti-DNA antibodies that express the dominant 16/6 idiotype--HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6--bound to glutaraldehyde-fixed platelets. In contrast, HF6-21/28, HF9-11/3, and polyclonal IgM bound poorly to platelets. [35S]Methionine was incorporated into HF2-1/17, and the interaction of the intrinsically radiolabeled HF2-1/17 with fixed platelets was evaluated in a solution phase radioimmunoassay. [35S]Methionine HF2-1/17 bound to fixed platelets and could be displaced by equivalent amounts of HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6. HF2-1/17 bound with greater affinity to fresh platelets and to thrombin-activated platelets than to glutaraldehyde-fixed platelets. Single-stranded DNA competed with platelets for the HF2-1/17 combining site. Treatment of fresh platelets with nuclease I, trypsin, chymotrypsin, and neuraminidase did not alter the binding of antibody to the platelet surface. No binding of antibody to phospholipid micelles was observed. Purified IgM autoantibodies did not inhibit platelet aggregation induced with ADP, thrombin, or ristocetin in platelet-rich plasma. These results indicate that the human IgM monoclonal anti-DNA autoantibodies that express the dominant 16/6 idiotype are polyspecific, bind to platelets, and interact with a platelet epitope that does not appear to involve DNA, protein, or sialic acid. These antibodies interact with platelets through the same sites responsible for antibody-DNA binding.
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PMID:Platelet binding properties of monoclonal lupus autoantibodies produced by human hybridomas. 406 19

Rt6 is a T cell-restricted GPI-anchored membrane protein and a member of the family of mono(ADP-ribosyl)transferases. One of the two murine Rt6 genes is deleted in NZW mice. This finding is reminiscent of the deletion of one of the TCR beta genes in the same mouse strain and it is an intriguing possibility that these gene deletions arose by a common genetic mechanism. The Rt6 locus retained by the NZW mouse (designated Rt6-1) is polymorphic among inbred strains of laboratory mice. The NZW mouse shows several strain-specific restriction fragment length variants in this Rt6 locus and five amino acid substitutions occur in the predicted native Rt6 polypeptide of the NZW mouse relative to the corresponding polypeptides of NZB and BALB/c mice. Whereas transcript levels of the two Rt6 genes appear to be normal in spleen and intestine of NZB mice, the corresponding tissues of NZW mice show reduced levels of transcripts from the Rt6 locus retained in this mouse strain. Moreover, reduced levels of Rt6 mRNA also occur in spleen and intestine of (NZB x NZW)F1 hybrid animals, indicating that F1 animals have inherited a dominant factor from the genetic background of the NZW mouse, resulting in low levels of Rt6 expression. It is conceivable that the alterations in the Rt6 genes of the NZW mouse and/or the factor(s) affecting defective Rt6 expression constitute part of the genetic contribution of the NZW mouse to the autoimmune lupus-like disease in (NZB x NZW)F1 animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defects in the structure and expression of the genes for the T cell marker Rt6 in NZW and (NZB x NZW)F1 mice. 754 15


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