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)

Anti-phospholipid antibodies (APA) are heterogeneous group of autoantibodies that target phospholipid or phospholipid-binding proteins. APAs were previously shown to induce several thrombotic states, including idiopathic recurrent spontaneous abortion (RSA). Unlike the contribution of the classical lupus anticoagulant (LAC) and anticardiolipin antibodies (ACA), the contribution of anti-beta2 glycoprotein 1 (beta2GPI) and anti-annexin V antibodies to RSA risk remain poorly understood. We assessed anti-beta2GPI and anti-annexin V IgM and IgG antibodies as RSA risk factors for RSA in 172 Tunisian women with >3 consecutive idiopathic pregnancy losses, together with 173 matched control women. The prevalence of anti-beta2GPI IgG (P=0.41, OR=1.64) and IgM (P=0.50, OR=1.70) were comparable between cases and controls. Higher anti-annexin V IgG (P=0.02, OR=5.28), but not IgM (P=0.25, OR=1.78), levels were seen in cases. Regression analysis showed that anti-beta2GPI IgM (OR=8.90; 95% CI=1.23-64.63) was associated with early RSA, while anti-annexin V IgG (OR=9.35, 95% CI=1.44-60.86) was associated with late RSA. For combined early + late RSA, the only variable selected was BMI (OR=0.93; 95% CI=0.87-0.99), and neither anti-annexin V nor anti-beta2GPI IgM and IgG were associated with early + late RSA. Anti-annexin V and anti-beta2GPI appear to be independent risk markers of RSA.
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PMID:Antibodies to beta2-glycoprotein I and annexin V in women with early and late idiopathic recurrent spontaneous abortions. 1682 14

Microparticles (MP) are small membrane-bound vesicles that circulate in the peripheral blood and play active roles in thrombosis, inflammation and vascular reactivity. While MP can be released from nearly every cell type, most investigation has focused on MP of platelet, leucocyte and endothelial cell origin. Cells can release MP during activation or death. Flow cytometry is the usual method to quantify MP; the small size of these structures and lack of standardization in methodology complicate measurement. As MP contain surface and cytoplasmic contents of the parent cells and bear phosphatidylserine, antibodies to specific cell surface markers and annexin V can be used for identification. Through various mechanisms, MP participate in haemostasis and have procoagulant potential in disease. MP contribute to inflammation via their influence on cell-cell interactions and cytokine release, and MP also function in mediating vascular tone. In several disease states characterized by inflammation and vascular dysfunction, MP subpopulations are elevated, correlate with clinical events, and may have important roles in pathogenesis. In the rheumatic conditions such as rheumatoid arthritis and systemic lupus erythematosus, MP are potentially important markers of disease activity and have an increasingly recognized role in immunopathogenesis. It is clear that MP play an important role in atherosclerosis, and study of these structures may provide insight into the link between chronic inflammatory conditions and accelerated atherosclerosis. As biomarkers, MP allow access to usually inaccessible tissues such as the endothelium. Further research will hopefully lead to interventions targeting MP release and function.
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PMID:The role of microparticles in inflammation and thrombosis. 1802 85

Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous 'dangerous' signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up-regulation of major histocompatibility complex (MHC) class II and co-stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low-density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein-deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro- or anti-apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up-regulate levels of HLA-DR and co-stimulatory molecule CD86. High oxLDL concentrations (50-100 microg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC 'danger' response induced by autologous plasma.
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PMID:'Danger' effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells. 1764 66

During recent years it has become evident that atherosclerosis is an inflammatory disease. Furthermore, immune reactions and especially autoimmunity, were demonstrated to modulate atherosclerosis in animal experiments. An interesting example of how autoimmune reactions can influence atherosclerosis and consequences thereafter, is systemic lupus erythematosus (SLE)-associated cardiovascular disease (CVD). Antithrombotic effect exerted by Annexin A5 (ANXA5) is thought to be mediated mainly by forming a mechanical shield over phospholipids (PLs) reducing availability of PLs for coagulation reactions. However, more specific properties of ANXA5 might be of importance for its antithrombotic function. Such examples include downregulation of surface-expressed tissue factor (TF), as well as upregulation of urokinase-type plasminogen activator (uPA) by ANXA5. Also, interaction of ANXA5 with ligands involved in hemostasis, such as sulfatide and heparin, has been demonstrated. We have recently described a novel mechanism potentially contributing to atherothrombosis in SLE, with ANXA5 binding to endothelium decreased in SLE, an effect caused by antiphospholipid antibodies (aPL). It may be hypothesized that ANXA5 can be effective as a treatment to prevent plaque rupture and atherothrombosis not only in SLE, but also in the general population prone to CVD. Antiatherothrombotic potential of ANXA5 deserves further attention and careful studies as the mechanism behind the majority of clinically significant cardiovascular ischemic disease is atherothrombosis, formed on an underlying vulnerable atherosclerotic lesion. It may be hypothesized that ANXA5 can be effective as a treatment to prevent plaque rupture and atherothrombosis not only in SLE, but also in a general population prone to CVD.
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PMID:Annexin A5 as a novel player in prevention of atherothrombosis in SLE and in the general population. 1789 75

The accelerated atherosclerosis that occurs in some patients with systemic lupus erythematosus (SLE) has a complex pathogenesis, including alterations in lipids, inflammation and the immune system. In this article, we review the evidence that peroxidase-related alteration of normal, protective high-density lipoprotein (HDL) converts them to pro-inflammatory HDL (piHDL), characterized by lower content of the cholesterol transport lipoprotein ApoA1 and impaired function of the antioxidant enzyme paroxonase, which prevents oxidation of low-density lipoprotein (LDL). Forty-five per cent of women with SLE have piHDL compared with 20% of patients with rheumatoid arthritis and 4% of healthy controls. The presence of piHDL increases risk for coronary artery events and carotid artery plaque. Another result of lipid oxidation in patients with SLE is generation of highly oxidized LDL and phospholipids (PL), probably stimulating antibodies to OxPL phospholipids. These antibodies along with promoting thrombosis also interfere with deposits of Annexin V onto endothelial cells, which probably promote increased instability of atherosclerotic plaque. Thus, piHDL and anti-OxPL promote plaque formation, plaque instability and thrombosis, accounting for some of the large increase in atherosclerosis and coronary artery events in SLE.
Lupus 2008 May
PMID:Atherosclerosis and systemic lupus erythematosus: the role of altered lipids and of autoantibodies. 1849 Apr 9

The aim of our study was to evaluate the clinical and HLA-class II allele associations of some anti-cofactor antibodies in a homogeneous group of European patients with SLE. One hundred thirty-six patients with SLE, fulfilling four or more of the ACR 1997 revised criteria for the classification of the disease, coming from 7 European countries, were enrolled consecutively. Anti-prothrombin (anti-PT), anti-annexin V (anti-AnnV), anti-protein C (anti-Cprot) and anti-protein S (anti-Sprot) were determined by using commercial ELISA kits. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 loci was performed by using PCR-SSOP method, carried out using digoxygenin (DIG) labeled probes. The prevalence of anti-AnnV, anti-PT, anti-Cprot and anti-Sprot was 19%, 10.4%, 4.4% and 8.1%, respectively. Twenty-seven % of anti-AnnV positive patients reported migraine vs 5.5% of anti-AnnV negatives (p = 0.003, but p not significant, odds ratio (OR) = 6.4, 95% confidence interval (CI) = 2-21). Anti-PT, anti-AnnV and anti-Sprot were positively associated with some HLA alleles, but pc was not significant. In this study we have shown that some HLA alleles carry the risk to produce antibodies against phospholipid-binding proteins, but these association need confirmation in other studies, because they have never been reported and appear to be weak associations.
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PMID:Anti-cofactor autoantibodies in systemic lupus erythematosus: prevalence, clinical and HLA class II associations. 1856 76

Pregnancy is widely authorized in systemic lupus erythematosus (SLE). Fertility is similar in SLE and in the general population although the age of menarche seems higher. Some cases of sterility might be attributed to SLE because of autoimmune ovaritis or antiphospholipid antibodies (aPL). These antibodies might lead to endothelial activation and thrombosis by influencing homeostasis, complement activation, inhibition of protein C and annexin V. They might have a deleterious effect on embryonic implantation by adhesion to the trophoblast, inhibition of invasion and placentation and decreased hCG production. The most important part of sterility seems secondary to the use of cyclophosphamide and might be prevented by acetate leuprolide administration. Maternal morbidity seems correlated to SLE activity (controlled by pregnancy planning), hypertension, preeclampsia, Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) syndrome, therapy and aPL. Hydroxychloroquine (HCQ) should be maintained throughout pregnancy. Aspirin is prescribed alone in patients with asymptomatic aPL and in addition to heparin if there is a history of thrombosis or fetal loss with aspirin. Fetal and neonatal morbidity correlate with prematurity, adverse effects or maternal steroid therapy and maternal anti-SSA antibodies with 1 to 2% risk of congenital atrioventricular block. Abnormal obstetrical echography-doppler examination is the best predictor of pregnancy outcome. Abnormal umbilical artery flow on the second trimester echodoppler examination and history of thrombophlebitis predict fetal or neonatal death. Abnormal uterine notch on the second trimester echodoppler examination predicts adverse pregnancy outcome. Except for the preventive therapy of congenital atrioventricular block, modalities of SLE pregnancy monitoring and therapy are now well established.
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PMID:[Pregnancy and systemic lupus erythematosus]. 1869 42

Apoptosis of lymphocytes is increased in patients with lupus. This may be pathogenic leading to increased load of autoantigens or may be a bystander effect of immune activation. A major unresolved issue is whether apoptosis is related to disease activity. Also its association with lymphocyte frequencies, anti-nucleosomal antibodies and serum IL 10 levels needs to be explored further. The aims of this study are to measure T- and B-lymphocyte apoptosis in patients with lupus and look at the effect of disease activity in a cross-sectional and longitudinal design and to determine frequency of T and B cells, level of anti-nucleosomal antibodies and serum IL 10 and assess their relationship with apoptosis. This study included 41 patients with SLE and 20 controls. A cutoff value of 4 in systemic lupus erythematosus disease activity index (SLEDAI) was used to separate active from inactive SLE. The frequency and degree of apoptosis of T and B lymphocyte were enumerated by flow cytometry using peripheral blood mononuclear cells (PBMCs) stained with CD3/CD19 and annexin V/PI. The data for T/B cell frequency are represented as % of these cells in the PBMC population, whereas percentage of apoptotic cells is out of total T or B cells. Serum anti-nucleosomal antibodies and IL 10 were assayed using ELISA. A repeat assessment of these parameters was carried out in 11 active patients when they became inactive. We found higher T-lymphocyte apoptosis in patients with SLE versus controls (14.8 +/- 9.2, 7.2 +/- 3.0; P < 0.05) and a lower frequency of T cells (72.7 +/- 12.6, 79.9 +/- 5.8; P < 0.05). T-lymphocyte apoptosis was higher in patients with active disease compared with inactive (18.5 +/- 11.3, 11.6 +/- 5.4; P = 0.05). Further, T-lymphocyte apoptosis directly correlated with SLEDAI (r = 0.37, P < 0.05) and inversely with T-cell frequency (r = -0.29, P < 0.05). Anti-nucleosomal antibodies correlated with SLEDAI but not apoptosis. On longitudinal follow-up, a decline in T-cell apoptosis was seen in patients with SLE, however this was not statistically significant. We confirmed a higher degree of apoptosis in T-lymphocytes in patients with SLE and found a direct correlation of T-cell apoptosis with disease activity. Patients had reduced T-cell frequency, which inversely correlated with T-cell apoptosis and may suggest a cause-effect relationship.
Lupus 2009 Aug
PMID:Increased T-lymphocyte apoptosis in lupus correlates with disease activity and may be responsible for reduced T-cell frequency: a cross-sectional and longitudinal study. 1957 2

Lupus anticoagulant (LA) and beta2-glikoprotein I (b2GPI) dependent anti-cardiolipin (aCL) are part of the diagnostic criteria both of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Anti-phospholipid antibodies (aPL) may also bind to other phospholipids and/or protein co-factors. In the present study, besides aCL and anti-b2GPI, antibodies directed against phosphatidylserine, prothrombin (PT) and annexin V (aANX) were measured in 85 randomly selected SLE patients, 14 suffering from secondary APS. LA was detected by hemostasis tests. Correlations were determined between rare aPLs and clinical manifestations, including thrombotic events. Anti-cardiolipin IgG was positive in 14 patients, aCL IgM in 8, anti-b2GPI IgG in 4 and IgM in 5 patients. LA was detected in nine cases. Seven patients were positive for anti-phosphatidylserine (aPS) IgG, nine for aPS IgM, while anti-PT (aPT) IgG was positive in nine cases. aPT IgM and anti-aANX were negative in all patients. Correlation was found between aPS and aCL antibodies. The frequency and concentration of rare anti-phospholipid/co-factor antibodies was higher in patients with secondary APS. The presence of such rare aPLs cumulated in APS patients, their presence increased the frequency of thrombotic events in the entire study population, furthermore in patients positive for LA or aCL. Rare anti-phospholipid/co-factor antibodies were found in 12% of an un-selected lupus patient population. Their presence was more frequent in patients with secondary APS, and further increased the risk of thrombotic complications.
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PMID:Identification of rare anti-phospholipid/protein co-factor autoantibodies in patients with systemic lupus erythematosus. 1962 89

Anti-phospholipid syndrome (APS) is defined based on both clinical findings (recurrent arterial and/or venous thrombosis and recurrent fetal loss) and laboratory evidence of persistent anti-phospholipid antibodies (anti-cardiolipin antibodies, anti-beta2 glycoprotein I antibodies, or LA activity). However, the precise mechanism responsible for arterial and/or venous thromboembolic complications in APS patients remains unclear. To clarify the association between the various types of anti phospholipid antibodies (aPLs) and thrombotic complications, we examined the prevalence of seven types of aPLs [anti-cardiolipin/beta2-glycoprotein I antibodies(anti-CL/beta2-GPI), anti-phosphatidylserine/prothrombin antibodies(anti-PS/PT), anti-beta2-glycoprotein I antibodies (anti-beta2-GPI), anti prothrombin antibodies (anti-PT), anti-protein C antibodies (anti-PC), anti-protein S antibodies(anti-PS), and annexin V antibodies(anti-AN)] in 168 patients with systemic lupus erythematosus (SLE). We confirmed that the presence of anti-CL/beta2-GPI, anti-PS/PT, and anti-beta2-GPI is closely related to arterial thrombosis, and that the presence of anti-protein S is closely related to venous thromboembolism. Furthermore, our in-vitro experiment suggests that anti-CL/beta2-GPI and anti-PS/PT may cooperate to promote platelet activation, and may be involved in the pathogenesis of arterial thrombosis. On the other hand, anti-protein S led to APC resistance, which may represent an important mechanism responsible for the development of venous thrombosis. Furthermore, our study showed that anti-CL/beta2-GPI causes a persistently high-level expression of tissue factor on monocytes, and this may increase the risk of atherosclerosis.
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PMID:[Advanced clinical laboratory studies in the graduate school of medicine--studies on pathogenic mechanisms of anti-phospholipid syndrome]. 1976 14


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