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)

We developed a sensitive and quantitative method for assaying lupus anticoagulants. The method was based on the inhibition of fibrin formation in a plasma-agarose gel plate, which was described as a method for assaying hemophilic factor VIII-inhibitor (Bird, 1975). The final concentration of plasma in agarose gel was set up 30% instead of 50%. Fibrin formation was stopped, when the clear zone of normal plasma as negative control disappeared and that of 0.039 units heparin as positive appeared. Then this improved the precision of measurement. The method was not only more sensitive than the dilute KPTT of a 1:1 mixture with normal plasma, but had no false positive. The standard curve was linear at heparin units from 0.039 to 100. The assay value could be estimated with heparin titer. This method seem to be useful for quantitative assaying and for determining low titer in lupus anticoagulants.
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PMID:[An assay of lupus anticoagulants by use of plasma-agarose gel]. 212 35

Markers of endothelial cell activation were measured in 28 patients presenting with various forms of limited or focal type cutaneous vasculitis. Plasma levels of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) and PAI-1 activity, fibrin plate, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and soluble thrombomodulin (sTM) were measured. In comparison with the control group (n = 20) there was a significant increase in t-PA:Ag, vWF:Ag and TF (P < 0.05, Mann-Whitney U-test) in the cutaneous vasculitis group. This study confirms that measurable degrees of endothelial activation occur in cutaneous vasculitis. Cutaneous vasculitis includes a diverse group of clinical conditions, which are associated with inflammatory changes in cutaneous blood vessels with local fibrin deposition. The aetiology and pathogenesis of the majority of these entities remain unknown. Causative mediators are thought to include immune complexes, anti-endothelial cell antibodies, cytotoxic lymphocytes and viruses. Histologically, immune complexes and complement are frequently detected on the vessel wall, and serologically anti-endothelial antibodies are often detected in patients with vasculitis and in systemic lupus erythematosus (SLE) which correlate with the severity of cutaneous vasculitis, arthritis and nephritis. Lymphocyte-mediated toxicity to endothelial cells has been reported in a small number of patients with giant cell arteritis and Takayasu's arteritis. The vascular endothelium plays a central part in the control of haemostasis. Under physiological conditions endothelial cells present an anticoagulant surface to blood constituents, partially due to surface expression of heparan sulphate and thrombomodulin (TM). Heparan sulphate binds antithrombin III (ATIII), thereby accelerating inactivation of intrinsic coagulation enzymes. Thrombomodulin is an endothelial cell surface glycoprotein which promotes anticoagulation by forming a complex with thrombin which then activates protein C. Activated protein C together with a cofactor, protein S, inactivates FVa and FVIIIa. von Willebrand factor (vWF) is synthesized by endothelial cells, stored in Weibel-Palade bodies and released into the circulation upon endothelial stimulation. vWF mediates the binding of platelets to the subendothelium and is the carrier molecule for FVIIIC. The endothelium controls fibrinolysis by producing t-PA and its inhibitor PAI-1. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) activate endothelial cells, causing a shift from an antithrombotic to prothrombotic state, including expression of tissue factor, increased synthesis of PAI-1 and decreased expression of TM. Fibrin deposition and intravascular thrombosis are seen in cutaneous vasculitis syndromes, suggesting local endothelial cell activation. The aim of this pilot study was to assess whether perturbation of the endothelium in cutaneous vasculitis could be detected in the patients' plasma samples. If so, further studies to assess any correlation in levels of these markers with disease activity might prove useful in the future.
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PMID:Endothelial cell activation in cutaneous vasculitis. 868 65

Antibodies to fibrin-bound tissue plasminogen activator (tPA) have been found in autoimmune diseases with vascular injury, such as systemic lupus erythematosus and scleroderma. The purpose of this study was to determine whether patients with primary pulmonary hypertension (PPH) have an immunogenetically determined response to fibrin-bound tPA. Antibodies to fibrin-bound tPA were determined in three patient groups: 45 adults with PPH, 41 children with PPH, and 40 children with anatomically large congenital pulmonary to systemic communications (PHT+shunt). The frequencies of the HLA class II (DRB1,3,4,5, and -DQB1) alleles in these three patient groups were compared with those of 51 healthy Caucasian control subjects. Fibrin-bound tPA antibodies were found in four of 45 (9%) adults with PPH, four of 41 (10%) children with PPH, and one of 40 (2.5%) children with PHT-shunt. HLA class II typing, which was available for seven of nine Caucasians with fibrin-bound tPA antibodies, revealed that six of seven (86%) patients typed HLA-DQ7 (DQB1*0301) and one typed HLA-DQ6. The 86% frequency of HLA-DQ7 in the antibody positive patients was significant compared with the 29% frequency in the healthy control subjects (p = 0.007, p corrected [pc] = 0.05, OR = 14.4). Of interest, these antibody-positive patients, although lacking antiphospholipid antibodies, shared an amino acid epitope, common to HLA-DQB1*06,07 and 08 subtypes, which was previously reported to be associated with the lupus anticoagulant. In conclusion, antibodies to fibrin-bound tPA and HLA-DQ7, and possibly the same epitope associated with the lupus anticoagulant, defined a small subset of children and adults with PPH.
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PMID:Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7. 900 24

Anti-beta2-Glycoprotein I (beta2GPI) autoantibodies are the prominent laboratory feature of Hughes syndrome. By prolonging some coagulation tests in the presence of exogenous phospholipids (PL), they behave as classical Lupus Anticoagulants (LA). We investigated the effect of 3 affinity-purified anti-beta2GPI IgG preparations from patients with Hughes syndrome on fibrin polymerization and fibrinolysis of normal plasma, measured by comparing the optical densities of assay mixtures in the presence of the autoantibodies or normal IgG. The presence of anti-beta2GPI IgG in diluted Russell Viper Venom Time (dRVVT) assays, carried out using a PL dilution of 1:8 or 1:64, resulted in a delay in the onset of polymerization by 30-40 and 60-70s, respectively. Fibrin polymerization was complete after 250s for both anti-beta2GPI IgG and normal IgG. The inhibitory effect of the anti-beta2GPI antibodies was not observed in the presence of excess PL, as expected for LA. Anti-beta2GPI IgG increased the plateau level of polymerization when dRVVT was performed in the presence of 1.5 nM recombinant tissue plasminogen activator, but did not impair the fibrinolytic process, which was almost complete after 250 min. The autoantibodies did not delay the onset of fibrin polymerization in tests carried out using recombinant tissue factor. On the contrary, the autoantibodies enhanced polymerization in prothrombin time assays, and accelerated it in tissue thromboplastin inhibition tests, with no effect on fibrinolysis. These data provide evidence that anti-beta2GPI LA may act as either anticoagulants or procoagulants in different in vitro coagulation tests.
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PMID:Effect of anti-beta2glycoprotein I Lupus Anticoagulants on fibrin polymerization and fibrinolysis. 1095 74

The present work was intended to study the process of fibrin formation and lysis and plasmin generation in a group of patients with recurrent miscarriage (RM), due to the presence of antiphospholipid antibodies (N = 10); as well as in women with RM without the antiphospholipid syndrome (APS) (N = 6), compared with those of a group of healthy women (N= 8). In the group of patients with APS, nine were positive for antibodies against cardiolipin (aCL), five for anti-beta2-glycoprotein I (anti-beta2GPI), four for both antibodies, and one for antibodies against prothrombin (aPT) and lupus anticoagulant (LA). Fibrin formation and lysis was followed by turbidity and plasmin generation using chromogenic substrate S2251. The polymerization curves from RM patients without APS and the LA patient showed an increased slope and maximum turbidity compared to those of the control group. The speed of lysis was higher in the LA patient (21 +/- 0) 10(-4) deltaOD/seg and the RM patients without APS (19.6 +/- 5.7) 10(-4) deltaDO/seg, compared to that of the control group (14.5 +/- 2.8) 10(-4) deltaDO/seg. Plasmin generation increased only in RM patients without APS (85 +/- 24%) against the control group (52 +/- 3%), p = 0.005. The changes observed in the fibrin polymerization and lysis process of women with RM without APS and LA seem to be related to their higher fibrinogen levels, while the increased plasmin generation was related to the patients' morbidity.
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PMID:[Effect of antiphospholipid antibodies on the formation and lysis of fibrin network in patients with recurrent miscarriage]. 2161 12

To find whether the plasma fibronectin (FN) molecular status can be useful to differentiate between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The expression of plasma FN domains was determined by ELISA using monoclonal domain-specific antibodies. FN molecular forms were revealed by immunoblotting and analyzed by densitometry. The following findings were found: (1) Mean values of (Fibrin-Heparin)FN concentration were lower in SLE and RA patients than in normal plasmas. The cut off points at 31 mg/l in SLE and at 45 mg/l in RA showed a sensitivity and specificity of 54, 55 and 75%, respectively. (2) Mean values of concentrations of (CBD)FN and (Ct)FN were lower in SLE than those in normal and RA plasmas. Quantified data showed the cut off points of (CBD)FN and (Ct)FN at 200 mg/l (58% of sensitivity, 56% of specificity) and 350 mg/l (58% of sensitivity, 58% of specificity) in SLE, as well as at 295 mg/l (52% of sensitivity, 51% of specificity) and 460 mg/l in RA (70% of sensitivity, 73% of specificity). (3) The plasma FN immunopatterns, characterized by the presence of high-molecular (260-310 kDa) and/or low-molecular (158-209 kDa) FN bands, were specific only for SLE samples. The analysis of plasma FN status revealed by its Fibrin-Heparin-, CBD- and Ct-domain reactivity with monoclonal antibody and immunoblotting can be helpful to differentiate the SLE in respect to RA and normal plasmas.
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PMID:Fibronectin molecular status determination useful to differentiate between rheumatoid arthritis and systemic lupus erythematosus patients. 2221 41