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 risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 +/- 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The -1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of -1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls (p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.
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PMID:The A-1087IL-10 allele is associated with cardiovascular disease in SLE. 1553 Sep 17

Although antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-beta(2)-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.
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PMID:Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis. 1558 39

Patients with rheumatoid arthritis (RA) have a two to five times increased risk of developing premature cardiovascular disease that shortens life expectancy by 5-10 years. Traditional risk factors known to promote and accelerate the progression of atherosclerotic lesions however, are often absent in patients with RA. Many similarities have emerged between the paradigm of inflammation in the pathogenesis of atherosclerosis and the well-established mechanisms of inflammation in the pathogenesis of RA. Hence it is intriguing to speculate that inflammation in RA is not confined to the joints but also present in the vessel wall. Indeed, low-grade inflammation and endothelial dysfunction play pivotal roles in the initiation, progression and propagation of the atherosclerotic process. While the healthy endothelium prevents adhesion of mononuclear cells, the defence mechanisms cease under the influence of cardiovascular risk factors and inflammation and they express adhesion molecules (selectins, vascular adhesion molecule-([VCAM-]1, intercellular adhesion molecule-[ICAM-]1) that promote the adherence of monocytes. This expression is induced by pro-inflammatory cytokines such as interleukin-(IL-)1beta and tumor necrosis factor-(TNF-)alpha, by C-reactive protein (CRP), and CD40/CD40 ligand interactions. As all of these factors are present at increased levels in the systemic circulation in RA, it appears possible that they might impact the endothelium as well. Further similarities include proteolytic enzymes such as matrix metalloproteinases (MMPs) that play a role in joint destruction as well as in destabilization and rupture of vulnerable atherosclerotic plaques. In addition, coagulation factors such as increased levels of tissue factor (TF), van Willebrand factor (vWF) and plasminogen activator inhibitor-(PAI-)1 are important in both, RA and CAD. Endothelial dysfunction has shown to correlate with cardiovascular prognosis in several studies, which indicates its clinical relevance. Endothelial function measurement is performed in the coronary or peripheral circulation (by venous occlusion plethysmography or flow-mediated dilation). Recent studies have demonstrated impaired endothelial function in patients with RA, already at early stages of the disease. Similar results are found in patients with systemic lupus erythematosus (SLE), indicating that inflammation per se may impair altering vascular function. This and more evidence supports the notion that inflammation plays a pivotal role in vascular dysfunction and may by these mechanisms explain at least part of the excess morbidity and mortality observed in RA and SLE. In light of the growing evidence of increased cardiovascular morbidity and mortality mostly independent of traditional risk factors, treatment strategies in RA should not only aim at relieving symptoms and inhibiting joint destruction but should have a beneficial effect on the vasculature to reduce cardiovascular events. Indeed, an improvement in endothelial function in RA was recently demonstrated by anti-TNF-alpha therapy and statins. Whether and to what degree the effects of anti-inflammatory strategies to improve endothelial function, which although clinically well established is still a surrogate, translate into clinical benefit for our patients with rheumatologic diseases needs to be determined in large-scale clinical trials some of which are now already under way.
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PMID:[Rheumatoid arthritis, inflammation, and atherosclerosis]. 1559 72

Although frequently asymptomatic, homozygous C2 deficiency (C2D) is known to be associated with severe infections and rheumatic disease. We describe the clinical findings in 40 persons with C2D from 33 families identified in Sweden over 25 years. Medical records covering 96% of the accumulated person-years were reviewed, giving a mean observation time of 39 years (range, 1-77 yr). Severe infection was the predominant clinical manifestation in the cohort: 23 patients had a past history of invasive infections, mainly septicemia or meningitis caused by Streptococcus pneumoniae, and 12 patients had repeated infections of this kind. Nineteen patients had at least 1 episode of pneumonia, and recurrent pneumonia was documented in 10 patients. Repeated infections occurred mainly during infancy and childhood. Systemic lupus erythematosus was found in 10 patients. Another 7 patients had undifferentiated connective tissue disease (n = 4) or vasculitis (n = 3). We found no correlation between susceptibility to invasive infection and rheumatologic disease. Cardiovascular disease occurred at a high rate, with a total of 10 acute myocardial infarctions and 5 cerebrovascular episodes in 6 patients. Causes of death among the C2D patients were infection (n = 5), acute myocardial infarction (n = 3), and cancer (n = 1). We suggest that severe infection may be the principal clinical manifestation of C2D. We also provide novel evidence for a possible role of C2D in the development of atherosclerosis consistent with findings in mannan-binding deficiency and experimental C3 deficiency. In addition, we confirm the well-known association between C2D and systemic lupus erythematosus.
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PMID:Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. 1564 97

There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.
Lupus 2004
PMID:Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus. 1564 46

Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Antiphospholipid syndrome (APS) is one of the most important causes of thrombosis in SLE. In addition, an association between hyperhomocysteinemia and increased cardiovascular risk has also been reported. Our aim is to analyse the association of thrombosis with plasma total homocysteine (ptHcy), antiphospholipid antibodies (aPL) and other vascular risk factors in SLE patients. Fasting plasma levels of ptHcy, vitamin B12, folate, total cholesterol and creatinine were measured in 117 SLE patients. Clinical and immunological data were obtained from our prospective computerized database. aPL-positivity was defined according to Sapporo criteria. There was no association between aPL and ptHcy. ptHcy was higher in patients with arterial (median 13.02 versus 10.16 micromol/L, P = 0.010) but not venous thrombosis. In the subgroup analysis, this association was only seen in aPL-negative patients. In logistic regression, aPL (OR 6.60, 95% CI 1.86-23.34) and ptHcy (OR 1.10, 95% CI 1.01-1.19) were independently associated with arterial thrombosis. However, when hypertension, smoking and plasma total cholesterol were added to the model, only aPL (OR 7.38, 95% CI 2.02-26.91) and hypertension (OR 7.70, 95% CI 2.33-25.39), but not ptHcy, remained independently related to arterial events. aPL was the only variable independently related to venous thrombosis (OR 7.68, 95% CI 1.60-36.86). ptHcy concentrations are higher in SLE patients with arterial thrombosis. No interaction between homocysteine and aPL was found. Raised ptHcy may be a marker of increased vascular risk in aPL-negative SLE patients. The role of homocysteine as a marker of vascular risk may depend on the presence of traditional risk factors, although a modest intrinsic effect cannot be entirely excluded.
Lupus 2004
PMID:Homocysteine, antiphospholipid antibodies and risk of thrombosis in patients with systemic lupus erythematosus. 1564 48

Most patients with systemic lupus erythematosus (SLE) are suitable candidates for renal transplantation. However, a number of them may present some disease-related problems. As cardiovascular disease is a leading cause of morbidity and mortality in SLE patients, a careful pretransplant cardiovascular screening is recommended. A search for antiphospholipid antibodies is also useful as the presence of these antibodies can cause an early graft thrombosis. The risk of recurrence of SLE nephritis after transplantation may range between 2 and 30%. In most cases recurrence is characterized by mild histologic lesions. Only rarely does it lead to graft failure. Postransplant immunosuppression does not differ from that used routinely. Whenever possible, a steroid-free immunosuppression should be scheduled to prevent iatrogenic toxicity in patients who have already received long-term steroid treatment. The results of kidney transplantation largely depend on the clinical conditions at transplantation. In patients with poor clinical status or receiving an aggressive immunosuppression it is advisable to postpone the transplant. When some selection criteria are respected, the results of renal trasplantation in SLE patients are at least as good as in other transplant recipients.
Lupus 2005
PMID:Renal transplantation in lupus nephritis. 1573 96

Dehydroepiandrosterone (DHEA) therapy is controversial due to sensationalized reports of epidemiologic studies and the over-the-counter availability of DHEA. Human clinical trials have investigated the potential efficacy of DHEA therapy in multiple conditions with resultant inconsistencies in findings. DHEA is unique compared with other adrenal steroids because of the fluctuation in serum levels found from birth into advancing age. The lower endogenous levels of DHEA and DHEA sulfate found in advancing age have been correlated with a myriad of health conditions. Also, some studies suggest gender-specific actions of endogenous and exogenous DHEA. We reviewed only pharmacokinetic studies and human clinical trials investigating the efficacy of DHEA therapy that were placebo-controlled as these provided the most reliable scientific basis for the evaluation of DHEA therapy. Pharmacodynamic studies suggest that doses of 30-50mg of oral DHEA may produce physiologic androgen levels, especially in women. These studies report a dose-dependent effect and lack of accumulation of serum androgen levels. Pharmacologic studies also reveal a gender-specific response to DHEA therapy such that testosterone levels are increased in women but not in men. Clinical trials suggest that 50mg of oral DHEA, but not <30mg, can increase serum androgen levels to within the physiologic range for young adults with primary and secondary adrenal insufficiency, possibly improve sexual function, improve mood and self-esteem, and decrease fatigue/exhaustion. Whereas DHEA replacement therapy may be effective in treating patients with adrenal insufficiency, human clinical trials investigating its efficacy in conditions such as systemic lupus erythematosus, HIV, Alzheimer disease, advancing age, male sexual dysfunction, perimenopausal symptoms, depression, and cardiovascular disease have not provided consistent findings.
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PMID:The use of dehydroepiandrosterone therapy in clinical practice. 1578 47

Despite recent advances, patients with systemic lupus erythematosus (SLE) still experience considerable morbidity and mortality. To try and improve their prognosis, varied novel biological interventions and immune manipulations are being developed. They may hold promise in particular for patients whose disease is organ-threatening and refractory to conventional treatment. In addition, awareness of the tendency of lupus patients to develop accelerated atherosclerosis as well as newly gained insights into the underlying mechanisms, may lead to better control of risk factors, earlier diagnosis of prevalent cardiovascular disease and more effective treatment. Infections also remain a significant threat that may be amenable to improved preventive measures. Evidence related to a better management of lupus patients by specialists, the need to address the impact of commonly associated stress and depression and other significant developments are also presented and discussed.
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PMID:The future of the treatment of systemic lupus erythematosus. 1589 1

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.
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PMID:SLE, atherosclerosis and cardiovascular disease. 1631 85


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