Antibodies, Anticardiolipin ; blood ; Autoantibodies ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; immunology ; beta 2-Glycoprotein I ; immunology

BACKGROUND: The presence of lupus anticoagulants (LA) is a strong risk factor for thrombosis in antiphospholipid syndrome. We investigated the usefulness of addition of silica clotting time (SCT) to the pre-existing dilute Russell's viper venom test (dRVVT) for detection of LA. Also, we analyzed differences in the thrombotic features and the characteristics of antiphospholipid antibodies between dRVVT and SCT. METHODS: A total of 167 patients positive for LA or anti-cardiolipin (anti-CL) antibody and 76 healthy controls were enrolled. The dRVVT and SCT were used for detection of LA. Anti-CL, anti-beta2-glycoprotein I (anti-beta2 GPI) and anti-prothrombin (anti-PT) antibodies were measured using commercial ELISA kits. RESULTS: In detection of thrombosis, the sensitivity of the combined test of SCT and dRVVT was 56.4%, which was higher than that of dRVVT alone (46.2%) or SCT alone (23.1%). The specificity of the combined test (80.9%) was comparable to that of dRVVT (81.9%). Also, odds ratio for predicting thrombosis was higher in the combined test than in dRVVT or SCT alone. When normalized LA ratio of the two tests was compared, the group of patients with higher ratio of SCT showed significantly higher prevalence of recurrent abortion and higher positivity of IgG types of anti-CL, anti-beta2 GPI and anti-PT than the group with higher ratio of dRVVT. CONCLUSIONS: Addition of SCT to dRVVT can improve the detection sensitivity of thrombosis in LA test. And the high normalized LA ratio of SCT may be a useful parameter for detection of recurrent abortion.
Adult ; Aged ; Antibodies, Anticardiolipin/analysis ; Antibodies, Antiphospholipid/analysis ; Blood Coagulation Tests/*methods ; Female ; Humans ; Immunoglobulin G/analysis ; Immunoglobulin M/analysis ; Lupus Coagulation Inhibitor/*blood ; Male ; Middle Aged ; Prothrombin/immunology ; Prothrombin Time/methods ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Silicon Dioxide/*chemistry ; Thrombosis/diagnosis ; beta 2-Glycoprotein I/immunology

This study is to explore the interventional effects of fluvastatin on anti-beta2GPI/beta2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-beta2GPI/beta2GPI, then the TF expression on THP-1 cells was detected by real-time quantitative PCR (RT-qPCR) or TF activity was detected by kit. TNF-alpha mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-kappaB p65 and inhibitory protein of NF-kappaB (IkappaB-alpha) were measured by Western blotting. The results suggested that the expression of TF and TNF-alpha on THP-1 cells was significantly up-regulated with treatment of anti-beta2GPI/beta2GPI complex (100 mg x L(-1)), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mg x L(-1)) could decrease TF (mRNA and activity) expression and the level of TNF-alpha (mRNA and protein) in THP-1 cells with anti-beta2GPI/beta2GPI complex. The expression of TF and TNF-alpha was shown in a concentration-dependent manner. Moreover, anti-beta2GPI/beta2GPI complex could downregulate IkappaB-alpha levels and increase the levels of phospho-NF-kappaB p65. And these effects of anti-beta2GPI/beta2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-kappaB signal transduction pathway, thereby inhibit the effects of anti-beta2GPI/beta2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-alpha.
Antigen-Antibody Complex ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Fatty Acids, Monounsaturated ; administration & dosage ; pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; pharmacology ; I-kappa B Proteins ; metabolism ; Indoles ; administration & dosage ; pharmacology ; Monocytes ; cytology ; metabolism ; NF-KappaB Inhibitor alpha ; Phosphorylation ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; Thromboplastin ; genetics ; metabolism ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; beta 2-Glycoprotein I ; antagonists & inhibitors ; immunology