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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In treating systemic lupus erythematosus, clinicians need to consider not only the organ involvement and the complications of therapy, but also associated conditions such as premature atherosclerosis and thrombosis. A variety of agents are now available to treat cutaneous disease, including the antimalarials and thalidomide. Controversy exists about the most appropriate immunosuppressive regimen in severe disease. Experience with using cyclosporine, mycophenolate mofetil, dehydroepiandrosterone, and intravenous immunoglobulin is increasing, but plasmapheresis has not been shown to be of benefit. Autologous bone marrow transplantation has been performed. The advent of the biological era, particularly with monoclonal antibodies, gives promise of more targeted therapy.
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PMID:Therapeutic advances in systemic lupus erythematosus. 974 59

During the past few years, changes in the spectrum of serious forms of systemic lupus erythematosus have been observed, and generally, the prognosis has improved. This results from a better understanding of the mechanisms of some visceral involvements (especially cerebral and cardiovascular), from the characterization of the antiphospholipid antibodies syndrome, and from a better management. As a result, kidney and central nervous system involvements are not the main causes of mortality any more. However, increasing survival leads to a higher frequency of some late complications, especially related to atherosclerosis.
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PMID:[Severe visceral involvement of lupus]. 978 Nov 32

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential. The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to beta2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.
Lupus 1998
PMID:Atherosclerosis and the antiphospholipid syndrome: a link unravelled? 981 92

A 37-year-old man sought medical advice because of an 8-year history of a slowly progressive dementing illness with no clinically apparent discrete strokelike episodes. Cognitive functioning was markedly, globally impaired without lateralizing or localizing features. Widespread livedo reticularis led to a diagnosis of Sneddon's syndrome. Antiphospholipid antibodies and lupus anticoagulant were negative. Magnetic resonance imaging showed widespread cerebral atrophy, cortical and subcortical cerebral infarcts, and extensive periventricular white matter abnormalities. Cerebral angiography revealed diffuse medium- and small-vessel occlusive disease, with numerous collaterals in the mid and distal circulation but no evidence of atherosclerosis or vasculitis. No other cause of a dementing illness was found. We postulate that our patient's dementia was due to the cumulative effects of multiple cerebral infarcts.
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PMID:Gradually progressive dementia without discrete cerebrovascular events in a patient with Sneddon's syndrome. 1059 61

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

There are two distinct histological manifestations of impaired placental implantation in humans--incomplete trophoblastic vascular invasion and atherosis. Both have been described to occur in pregnancies affected by a variety of disorders such as preeclampsia, fetal growth restriction, systemic lupus erythematosus, and diabetes. Our purpose was to integrate recent developments in the understanding of implantation site disorders into a pathophysiological scenario that interrelates these placentation disorders and associated pregnancy complications. Sources were identified from a MEDLINE search of English-language articles published from 1966 to 1997. Additional sources were identified from references cited in relevant reports. We selected articles relating to the following topics: atherosis, implantation site disorders, trophoblastic invasion, preeclampsia, fetal growth restriction, implantation site development, atherosclerosis, and endothelial activation-damage. A contemporary version of normal placentation, including vascular adaptation, was reviewed with comments on normal trophoblastic differentiation and vascular invasion. Specific abnormalities of the implantation site, including atherosis and incomplete trophoblastic invasion, were discussed in the context of placental site hypoperfusion and the association with pregnancy complications. It was concluded that atherosis and incomplete trophoblastic invasion may be both a consequence and a cause of placental site hypoperfusion resulting in the development of preeclampsia and a variety of other pregnancy disorders.
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PMID:Atherosis revisited: current concepts on the pathophysiology of implantation site disorders. 1007 38

Antiphospholipid Syndrome (APS) was first described by Hughes and sometimes called as Hughes syndrome. Recent studies revealed that the antigen to anticardiolipin antibody (aCL) is not cardiolipin itself but co-factor beta 2-GPI which expresses its epitope when it combines cardiolipin or gets oxidized. Lupus Anticoagulant is now possibly considered as anti-prothrombin antibody. Livedo including Snedden syndrome, pulmonary hypertension and skin ulcer became considered as the part of symptoms of this disease. In ISAPA 1998, it is reported from several laboratories that IgA aCL is also pathogenic to thrombosis as well as IgG aCL. Atherosclerosis is also accelerated by aCL. Catastrophic APS is rare but fatal, reported 3 cases in Japan and 50 cases in the world.
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PMID:[Antiphospholipid syndrome]. 1007 9

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.
Lupus 1999
PMID:Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE. 1019 9

Cardiovascular manifestations are common in systemic lupus erythematosus (SLE). Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascular disease, especially atherosclerosis, and cross-reacts with antibodies to cardiolipin (aCL). beta 2-GPI is a plasma protein participating in the coagulating cascade, and is also cofactor for aCL, and some aCL have been shown to be directed against beta 2-GPI and/or complexes between beta 2-GPI and phospholipids. Lysophosphatidylcholine (LPC) is a phospholipid present both in oxLDL and in damaged endothelium, and we recently showed that LPC is involved in the antigenicity of oxLDL. Antibodies to endothelial cells (aEC) correlate with diseases activity in SLE and vasculitis, and we recently showed that aEC are enhanced in cardiovascular disease such as borderline hypertension and early atherosclerosis. aEC were determined using EC from adult V. Saphena Magna. Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184 patients with SLE compared with 85 healthy controls. There was a close correlation between aoxLDL, aCL, aLPC, a beta 2-GPI and aEC. Binding of sera to EC was competitively inhibited by beta 2-GPI, LPC and oxLDL. Taken together, the data indicate that EC share antigenic epitopes with beta 2-GPI and with oxLDL, especially LPC. Phospholipids in EC membranes may thus be antigenic epitopes. beta 2-GPI may bind to these phospholipids, and become an autoantigen. LPC is formed by oxidation of phospholipids and/or proinflammatory factors leading to activation of phospholipase A2, and the findings indicate the potential role of both lipid oxidation and phospholipase A2 in SLE.
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PMID:Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus erythematosus. 1019 34

Systemic Lupus Erythematosus (SLE) patients experience premature atherosclerosis. A deranged lipid metabolism and use of immunosuppressive medications accounts partially for the accelerated process. The role of autoimmunity in atherosclerosis has recently been highlighted. Autoantigenic determinants thought to play a role in the development of atherosclerosis include: modified lipoproteins, heat shock proteins and beta2-glycoprotein I (a target of 'autoimmune' anticardiolipin antibodies). In this present work we determined autoimmune markers which may be associated with premature atherosclerotic process found in SLE patients. We have found that antibodies to oxLDL were raised in the sera of lupus patients and cross-reacted with cardiolipin and with beta2GPI. OxLDL containing immune-complexes of the IgG and IgM isotypes were both elevated in the SLE patients as compared with healthy controls. Patients with high Lipoprotein (a) concentrations (>30 mg/dl) had higher levels of IgM oxLDL-containing immune-complexes. IgM but not IgG anti-HSP-65 antibodies were elevated in the lupus patients and levels of oxLDL containing immune-complexes correlated positively with the presence of anti-HSP 65 antibodies. Lysophosphatidylcholine (LPC) is a peroxide-derivative formed during LDL oxidation, was shown to evoke a humoral response in healthy subjects. Antibodies to lysophosphatidylcholine of the IgG but not the IgM isotype were reduced in SLE patients compared with controls, suggesting it may be 'consumed' into oxLDL containing immune complexes. Therefore, SLE patients exhibit a humoral autoimmune response towards the antigenic candidates incriminated in the progression of atherosclerosis. These findings may help identify factors that are involved in accelerating atherogenesis in SLE patients.
Lupus 1999
PMID:Atherosclerosis-related markers in systemic lupus erythematosus patients: the role of humoral immunity in enhanced atherogenesis. 1034 15


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