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)

The study of antiphospholipid (aPL) antibodies has been greatly developed in recent years and conclusive evidence now exists concerning the correlation between aPL and clinical signs such as thrombosis, thrombocytopenia, abortion, and fetal loss. Several hypotheses have been put forward concerning the pathogenic mechanism of aPL, but none has received final confirmation from experimental data. Many studies have been devoted to characterizing the antigens recognized by the different aPL autoantibodies and to a cofactor involved in the binding of autoantibodies and phospholipids; this cofactor has been identified as an apolipoprotein, the beta 2 glycoprotein I (beta 2GPI) or APO-H. Direct evidence now exists which suggests that both the beta 2GPI and the phospholipid comprise the epitope to which aPL are directed. On the other hand anti-beta 2GPI antibodies have been identified in sera of patients suffering from SLE and primary Antiphospholipid Syndrome. beta 2GPI is normally present in human plasma/serum and possesses numerous inhibitory functions in multiple coagulation pathways. The amino acid sequence of beta 2GPI has been identified and found to consist of five repeating units that belong to the complement control protein (CCP) superfamily. This development of knowledge related to aPL has followed three steps respectively: 1. the standardization of the techniques of detection: 2. identification of the clinical signs related to the autoantibodies: and finally 3. the discovery of a new player, the beta 2GPI cofactor.
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PMID:A new player in the antiphospholipid syndrome: the beta 2 glycoprotein I cofactor. 130 77

Patients treated with corticosteroids often have a dyslipoproteinemia characterized by elevated plasma levels of triglyceride and low density lipoprotein cholesterol and/or decreased levels of the high density lipoprotein2 fraction of high density lipoprotein cholesterol. This study was undertaken to determine if such patients also have elevated apolipoprotein-B (apoB) levels and/or abnormalities of the activities of the triglyceride lipases in postheparin plasma. Plasma lipoprotein levels and the postheparin activities of hepatic lipase and lipoprotein lipase were measured in 28 women with systemic lupus erythematosus (SLE) who were treated with prednisone, 10 women with SLE not treated with prednisone, and 15 normal women. The prednisone-treated group had higher mean plasma levels of triglyceride [2.06 +/- 1.3 (+/- SD) vs. 1.15 +/- 0.35 and 0.95 +/- 0.46 mmol/L; P less than 0.01], low density lipoprotein cholesterol [3.41 +/- 1.4 (+/- SD) vs. 2.79 +/- 0.67 and 2.84 +/- 0.70 mmol/L; P less than 0.01], and apoB [1.16 +/- 0.35 (+/- SD) vs. 0.82 +/- 0.13 and 0.76 +/- 0.22 g/L] than the other 2 groups. Forty-three percent of the prednisone-treated group had apoB levels of 1.20 g/L or more compared to 7% of normal subjects and none of the untreated SLE group (P less than 0.05). However, of the 12 prednisone-treated patients with elevated plasma apoB levels 5 had normal plasma lipid levels. There were no differences in the postheparin lipase activities among the 3 groups. These data indicate that corticosteroid-treated patients have elevations in apoB as well as hyperlipidemia. The lipoprotein abnormalities may explain the increased risk of atherosclerosis reported in these patients.
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PMID:Elevated apolipoprotein-B levels in corticosteroid-treated patients with systemic lupus erythematosus. 341 Sep 32

The increased incidence of atherosclerotic coronary artery disease in patients with systemic lupus erythematosus (SLE) may be due to a dyslipoproteinemia caused by corticosteroid administration. To determine whether lipoprotein lipid levels are abnormal in SLE and the relation of lipoprotein levels to corticosteroid use, lipid and apolipoprotein levels were measured in 46 female patients with SLE and 30 matched control subjects. The patients with SLE had higher levels of plasma triglyceride (134 versus 73 mg/dl; p less than 0.001), cholesterol (201 versus 168 mg/dl; p less than 0.001), and low-density lipoprotein cholesterol (121 versus 94 mg/dl; p less than 0.001) than control subjects. The levels of high-density lipoprotein cholesterol, high-density lipoprotein subfraction 3 cholesterol, and apolipoprotein Al were similar in the two groups, but high-density lipoprotein subfraction 2 cholesterol was lower in the patients with SLE (10.2 versus 18.2 mg/dl; p less than 0.001). When patients with SLE treated with prednisone (n = 32) were compared to patients with SLE not treated with prednisone (n = 14), the former had higher triglyceride (158 versus 87 mg/dl; p less than 0.001), cholesterol (214 versus 170 mg/dl; p less than 0.001), and low-density lipoprotein cholesterol (130 versus 103 mg/dl; p less than 0.001) levels. The patients with SLE not treated with prednisone had lipid levels similar to those in control subjects except that high-density lipoprotein cholesterol was lower (49.7 versus 59.0 mg/dl; p less than 0.05). The daily prednisone dosage in the treated patients with SLE correlated with levels of cholesterol (r = 0.38, p less than 0.02), high-density lipoprotein cholesterol (r = 0.40, p less than 0.02), and high-density lipoprotein subfraction 3 cholesterol (r = 0.47, p less than 0.01). Thus, female patients with SLE have a dyslipoproteinemia of the type that would place them at an increased risk for coronary artery disease. Corticosteroids, used in the treatment of SLE, seem to play a role in the pathogenesis of the observed lipoprotein abnormalities.
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PMID:Dyslipoproteinemia in systemic lupus erythematosus. Effect of corticosteroids. 366 87

Lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine were studied in 18 female patients with systemic lupus erythematosus (SLE) with mild or inactive disease. Patients were case matched (200-400 mg hydroxychloroquine daily vs no hydroxychloroquine) on several factors including daily corticosteroid dose in this cross sectional study. All had normal menstrual cycles; none smoked, used alcohol, were taking lipid altering medications or had other concurrent diseases. Patients taking hydroxychloroquine had 35-54% lower total triglyceride, VLDL-triglyceride, LDL-triglyceride, HDL-triglyceride, VLDL-cholesterol, and apolipoprotein CIII levels (p < 0.03). These results are encouraging in that hydroxychloroquine, in addition to being useful for alleviating the primary symptoms of SLE, may also be useful for ameliorating the adverse effects of corticosteroid therapy on triglyceride-rich lipoprotein metabolism.
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PMID:The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus. 849 61

Gemfibrozil improves lipid and apolipoprotein profiles, particularly very low density lipoprotein (VLDL) triglyceride and high density lipoprotein (HDL) cholesterol levels, in patients with dyslipidaemia when administered at a total daily dose of 900 or 1200 mg. As demonstrated by the Helsinki Heart Study, these effects result in a reduction in some risk factors for coronary heart disease (CHD) and also a 34% reduction in the incidence of this disease after 5 years compared with placebo. Limited data suggest that gemfibrozil has beneficial effects on the fibrinolytic system and may slow the progression of atherosclerosis. Gemfibrozil has shown efficacy in the treatment of patients with type IIa, IIb, III, IV or V dyslipidaemia or hypoalphalipoproteinaemia, especially in patients with elevated triglyceride and low HDL cholesterol levels. It is also effective in patients with non-insulin-dependent diabetes mellitus (NIDDM) and dyslipidaemia and has no detrimental effects on glycaemic control. A small number of studies also showed gemfibrozil to be effective for the control of dyslipidaemia associated with renal failure, transplantation, nephrotic syndrome, arterial occlusive disease or systemic lupus erythematosus. However, patients with pre-existing CHD do not appear to derive the same benefits (reduced CHD mortality) from gemfibrozil therapy as these other patients, although results are based on studies of limited size and number. In general, gemfibrozil has at least similar efficacy to bile acid sequestrants and other fibric acid derivatives. Comparisons with HMG-CoA reductase inhibitors show these agents to produce different effects on lipid profiles from gemfibrozil. Thus, gemfibrozil would be expected to be superior in some patients (those with elevated triglyceride or VLDL cholesterol levels), but HMG-CoA reductase inhibitors should have greater benefits in those with elevated low density lipoprotein cholesterol levels. Thus, in patients with elevated triglyceride levels and low HDL cholesterol levels, and, particularly in patients with NIDDM, gemfibrozil is a useful treatment option, which has been shown to reduce the risk of CHD in middle aged men. However, limited available data prevents the accurate comparison of this agent with HMG-CoA reductase inhibitors in patients with this lipid profile.
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PMID:Gemfibrozil. A reappraisal of its pharmacological properties and place in the management of dyslipidaemia. 873 20

In examining reasons for premature atherosclerosis in systemic lupus erythematosus (SLE), we previously reported low levels of the cholesterol transport protein apolipoprotein A1 (apoA1) in these patients, and specific antibodies to purified apoA1 were identified in the sera of 5 out of 30 lupus patients. The current study was initiated to determine whether these antibodies are common in lupus patients. 520 serum samples from 175 patients with SLE or primary antiphospholipid syndrome (PAPS) were tested for antibodies to purified apoA1. Positive sera were retested for binding to apolipoprotein incorporated into reconstructed nascent or mature high-density lipoprotein (HDL). Autoantibodies to apoA1 were found in 32.5% of patients with SLE and 22.9% of patients with PAPS, associated with the presence of aPL (anti-beta2 glycoprotein-1, anti-beta2 GP1) antibodies. When reconstructed, nascent and mature HDL molecules were compared as antigen-containing environments, positive sera reacted best to apoA1 embedded in mature HDL molecules. This report confirms the high prevalence of antibodies to apoA1 in patients with systemic lupus and suggests a high affinity of these antibodies for mature HDL.
Lupus 1998
PMID:Frequency of antibodies to the cholesterol transport protein apolipoprotein A1 in patients with SLE. 969 40

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL) induced in patients with antiphospholipid syndrome and their antigenic epitopes are cryptic. The epitopes appear on the surface of beta2-GPI molecule only when beta2-GPI interacts with lipid membranes containing negatively charged phospholipids or polyoxygenated polystyrene surface. Our data also indicated that CuSO4-oxidized low density lipoproteins (oxLDL) are subsequently targeted by beta2-GPI and aCL; however, malonedialdehyde (MDA)-modified LDL were recognized neither by beta2-GPI nor aCL. Beta2-GPI binding to LDL was rapidly increased by incubation with CuSO4. Oxidation of lipoproteins was accompanied with the increment of thiobarbituric acid-reactive substances (TBARS) and denature of apolipoprotein. Ligands on LDL for beta2-GPI seemed to be intermediate oxidative derivatives which were extractable into the chloroform phase by Bligh and Dyer's extraction, but not MDA. Further, immune responses against beta2-GPI, as an anti-atherogenic protein, were demonstrated to induce atherogenic effect in in vitro oxLDL uptake by macrophages.
Lupus 1998
PMID:Antiphospholipid antibodies and atherosclerosis. 981 91

The paper summarizes the results of over 30-year studies dealt with dyslipidemias and autoimmune diseases. The teaching of the antiphospholipid syndrome (APS) has aroused interest in the problem. The experience gained shows changes in the blood cholesterol transport system. Patients with systemic lupus erythematosus (SLE) have higher levels of low density lipoprotein cholesterol and lower concentrations of high density lipoprotein (HDL) cholesterol, apolipoprotein A than the controls. The quantitative and qualitative changes in particles result in decreased acceptance of cholesterol from the membrane of a cell and tissues, which promotes the development of vascular diseases. Lipoprotein (a) may be an additional risk factor for thrombosis chiefly of coronary arteries, in patients with SLE and APS. Increased levels of oxidized low density proteins having atherogenic activity were found mainly in patients with SLE. The use of corticosteroids causes the changes in the spectrum of blood lipids, which together with other factors (thrombosis, vasculopathy, thrombocytopenia, etc.) create good conditions for the development of atherosclerosis, which determines the necessity of correcting the parameters of blood lipid transport not only to prevent vascular disorders but to improve the general life prognosis in SLE patients.
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PMID:[Dyslipidemias and autoimmune diseases]. 998 60

Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterised by the production of autoreactive T cells and autoantibodies that may affect every organ system. It has long been established that there is a close association between cholesterol- rich lipoproteins (such as low-density lipoprotein-cholesterol) and cardiovascular disease in patients with SLE. In this study, we evaluated total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLD-cholesterol, apolipoprotein A-1, apolipoprotein B, and cholesterol-rich serum lipoprotein(a) [Lp(a)], which is accepted to be an independent risk factor for cardiovascular disease and for atherosclerosis, in 24 patients (mean age +/- SD 31.4 +/- 9.7 years, range 16-47, 22 F) with active SLE. Twenty-six healthy age- and sex-matched (mean age +/- SD 29.7 +/- 11.3 years, range 18-49 years, 22 F) subjects were included as a control group. In patients with SLE Lp(a) levels, total cholesterol, triglycerides and VLDL-cholesterol were found to be higher and HDL-cholesterol, apolipoprotein A-1 to be lower than those of controls. In conclusion, because serum Lp(a) levels are significantly higher (P<0.01) in patients with SLE, these patients have a risk of developing cardiovascular disease and atherosclerosis. Patients with SLE should be followed up with this in mind.
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PMID:Serum lipoprotein(a) level and its clinical significance in patients with systemic lupus erythematosus. 1244 39

The etiology of chronic immuno-inflammatory diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and atherosclerosis is far from being elucidated. It is generally accepted that multiple factors are involved in the development of such pathologies, including factors of genetic susceptibility that interact in complex ways with diverse environmental factors, i.e. gender, nutrition, environment, etc. Furthermore, infection has often been pinpointed as playing a causal role. However, no distinctive pattern has yet emerged from the tremendous number of compiled results that would provide a generally acceptable hypothesis of the etiology of immuno-inflammatory diseases, and the possibility of a persistent antigenic stimulus arising from an infection cannot be confirmed or refuted. At the cellular level, chronic inflammation is characterized by the infiltration of immuno-inflammatory cells into the target tissue, which mostly precedes tissue damage. At the inflammatory site, monocytes and T lymphocytes are in close proximity. We have demonstrated that contact-mediated activation of monocytes by stimulated T lymphocytes is a major stimulus triggering the production of large amounts of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) whose importance in chronic inflammation is well known. We recently established that high-density lipolipoprotein (HDL)-associated apolipoprotein (apo) A-I is a specific inhibitor of cytokine production in monocyte-macrophages upon contact with stimulated T cells. HDL-associated apo A-I is a negative acute-phase protein, i.e. a protein whose level is lowered by more than 25% during the acute phase. This review aims at highlighting the fact that HDL-associated apo A-I might play the role of a constitutive anti-inflammatory factor. The decrease of plasma levels of HDL-associated apo A-I upon acute inflammation may be a sign of the possible development of chronic inflammation, i.e. individuals presenting with risk factors might develop chronic inflammatory diseases after infection. We thus hypothesize that HDL-associated apo A-I might be the missing link between infection and chronic inflammation.
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PMID:High-density lipoprotein-associated apolipoprotein A-I: the missing link between infection and chronic inflammation? 1284 67


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