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)

Vascular damage in systemic lupus erythematosus (SLE) occurs through vasculitis, premature atherosclerosis, and hypercoagulability (predominantly due to the antiphospholipid antibody syndrome). In the Hopkins Lupus Cohort, a prospective cohort study, the incidence of thrombosis is 2 per 100 person-years of follow-up. Markers of immune-complex mediated injury (high anti-dsDNA and low C3), atherosclerosis (hypertension, hyperlipidemia, homocysteine) and antiphospholipid antibodies (lupus anticoagulant or anticardiolipin) are independent predictors of thrombosis. Hydroxychloroquine use is protective against future thrombosis.
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PMID:Thrombosis and systemic lupus erythematosus: the Hopkins Lupus Cohort perspective. 879 94

We report a patient who had an ischemic stroke aged 22 years, an inherited type I protein C deficiency and a heterozygous genotype of prothrombin gene 20210A. In view of recent reports of an increased risk for ischemic cerebral vascular disease in patients with the prothrombin 20210A mutation, we suggest that many of the reported cases of ischemic stroke and protein C deficiency may have had additional prothrombotic disorders such as the prothrombin mutation. The current data concerning the magnified risk for stroke in patients with the prothrombin 20210A mutation suggests the need to study all patients with premature stroke for this mutation and the other risk factors for thrombosis. This would include homocysteine, lupus inhibitor, anticardiolipin antibodies, and possibly the natural inhibitors of coagulation. It is possible that patients with the prothrombin 20210A mutation and ischemic cerebral vascular disease would benefit from long-term anticoagulation therapy in a similar way to patients with the antiphospholipid syndrome.
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PMID:Ischemic stroke in a young patient with protein C deficiency and prothrombin gene mutation G20210A. 989 Jul 20

We describe a case of a 28-year-old man who developed an extensive spontaneous deep venous thrombosis. Testing revealed heterozygotic factor V Leiden mutation, and the presence of both lupus anticoagulant (LA) and elevated IgM anticardiolipin antibody (ACA). Several family members were found to be heterozygous for factor V Leiden. A paternal aunt had the factor V Leiden mutation, an elevated plasma homocysteine and a borderline increased IgG ACA level. No other family member had a history of a venous thrombotic event. This case illustrates that evaluation of young patients who present with venous thrombosis should be performed for both hereditary and acquired thrombophilic defects. The family studies suggest that the presence of a lupus anticoagulant may be more clinically significant than elevated ACA in risk assessment. Although screening family members when the proband carries factor V Leiden is controversial, psychological reassurance of those who test negative and simple advice on occupations or social habits (e.g., smoking) for those who test positive may be important benefits.
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PMID:Spontaneous venous thrombosis in a young patient with combined factor V Leiden and lupus anticoagulant. 1046 79

The alanine/valine (A/V) gene polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing remethylation of homocysteine, has been reported and the VV genotype is associated with increased plasma homocysteine levels as a result of the reduced activity and increased thermolability of this enzyme. Although previous studies have suggested that the VV genotype is a risk factor for arterial occlusive disease, whether the VV genotype is a risk factor for venous thrombosis is still controversial. Here we screened 72 Japanese patients with deep venous thrombosis (DVT) and 85 controls for this mutation, and we measured plasma levels of homocysteine to determine whether the thermolabile variant with the VV genotype is a risk factor for DVT in a Japanese population. Of the 72 patients with DVT, 10 (13.9%) were found to be homozygous for the VV genotype, and in 6 (7.0%) of 85, control individuals and the difference was not significant (odds ratio=2.12, 95% CI=0.73-6.16, p=0.19). When we divided the DVT patients into subgroups, with and without predisposition of thrombophilia, including deficiencies of proteins C and S, plasminogen, and lupus anticoagulant, the prevalence of the VV genotype in DVT patients with predisposition was significantly higher than that of the normal controls (odds ratio=5.99, 95% CI=1. 56-22.96, p=0.01). However, the prevalence of the VV genotype in DVT patients without predisposition was not significantly different from that of the normal controls (odds ratio=1.20, 95% CI=0.32-4.47, p=0. 75). The plasma homocysteine levels in patients with DVT (11.6+/-5.2 nmol/ml) was not significantly different from that of the control subjects (11.6+/-3.7 nmol/ml). Individuals with the VV genotype showed higher plasma homocysteine levels (15.4+/-6.9 nmol/ml) than did individuals with the AV genotype (11.2+/-3.7 nmol/ml, p=0.009) or in individuals with the AA genotype (11.1+/-4.2 nmol/ml, p=0.004). Serum folate and vitamin B12 levels were not correlated with the plasma homocysteine levels. In conclusion, even though homozygosity for the VV genotype of the MTHFR gene was associated with higher plasma homocysteine levels, we found no association between plasma levels of homocysteine and DVT or between the genotype of the MTHFR gene and the DVT incidence. However, we found that the VV genotype of the MTHFR gene is a risk factor for DVT only when combined with the predisposition of thrombophilia.
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PMID:Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia. 1070 28

Coronary artery disease (CAD) is a major cause of morbidity and mortality in SLE, including the Hopkins Lupus Cohort. Currently, 9% of the cohort have had clinical evidence (angina or myocardial infarction) of CAD. In our initial prospective study we found that duration of prednisone, hypertension, hyperlipidemia and obesity were risk factors for later CAD. We can now extend that list to include age, male sex, elevated homocysteine, renal insufficiency and antiphospholipid antibodies. Many of the risk factors are amenable to intervention, but the timing of intervention, and the effectiveness of intervention, must be determined.
Lupus 2000
PMID:Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. 1080 83

We examined the relationship between placental histology and thrombophilia status in women who were admitted with severe pre-eclampsia/eclampsia, placental abruption, intrauterine growth restriction or unexplained stillbirth. All women had thrombophilia screen at least 10 weeks after delivery (antithrombin III, protein C, protein S, activated protein C resistance, anticardiolipin antibodies, lupus anticoagulant, fasting plasma homocysteine and specific mutations to methylenetetrahydrofolate reductase C677T, G20210A prothrombin gene and factor V Leiden. Placental histology reports were examined to identify the frequency of thrombotic lesions in the placenta including fetal stem vessel thrombosis, fetal thrombotic vasculopathy, placental infarction, perivillous fibrin deposition, intervillous thrombosis and placental floor infarction. During a 17 month period, a cohort of 79 women met the study criteria. Thirty (70%) out of 43 women with abnormal thrombophilia screen had abnormal placental histology. Twenty-eight (78%) out of 36 women with negative thrombophilia screen had abnormal placentae. No specific histological pattern could be identified when thrombophilia positive and thrombophilia negative groups were compared. We propose that there is a poor correlation between thrombophilia status and pathological changes of the placenta in women with severe pregnancy complications.
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PMID:Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? 1115 44

Long-term survival of renal transplant recipients appears to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. In order to investigate the prevalence of new hemostasis-related risk factors for venous and arterial thrombosis, we investigated 63 renal transplant recipients and 66 age- and sex-matched control subjects. We assayed antiphospholipid antibodies [lupus anticoagulant (LA) and anticardiolipin antibodies (aCL)], lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and total homocysteine (tHcy) levels. We found a significantly higher prevalence of positivity for LA (P < 0.001); no difference was detected in the prevalence of aCL between patients and controls. PAI-1 levels were significantly higher in renal transplant recipients than in controls [12.3 IU/ml (2-45.5) vs 7.9 IU/ml (4-18.0); P < 0.0001] with an odd ratio (OR) of 11.8 (4.9-28.5) in univariate analysis and of 5.8 (2.1-15.4) in multivariate analysis. Lp(a) levels were higher in patients then in controls [159 mg/l (1-992) vs 100.5 mg/l (10-412); P < 0.005] with an OR of 5.9 (1.9-18.4) in univariate analysis and of 3.5 (0.9-13.4) in multivariate analysis. Fasting levels of tHcy were significantly higher in renal transplant recipients [7.0 micromol/l (4.0-68) vs 8.1 micromol/l (2.0-24.0); P < 0.00001] with an OR of 40.4 (14.7-111) in univariate analysis and of 33.1 (11.1-115.5) in multivariate analysis. After methionine loading test, we documented levels of tHcy above the 90th percentile of controls in 60/63 patients (95%). Finally, we found a significant correlation between tHcy and PAI-1 plasma levels (r = 0.76; P < 0.000001). Our results show a high prevalence of hemostasis-related risk factors for arterial and venous thrombosis in renal transplant recipients, suggesting the need for the investigation of these patients for the presence of these risk factors in order to improve their long-term survival and to tailor therapy.
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PMID:Risk factors for cardiovascular disease in renal transplant recipients: new insights. 1111 46

Antiphospholipid antibodies (aPL), especially lupus anticoagulant (LAC), characterize systemic lupus erythematosus (SLE) patients at increased risk for arterial and venous thromboembolic complications. It has been reported that purified human anti-phospholipid antibodies cause endothelial cell activation in in vitro experiments. In order to investigate whether increased endothelial cell activation is associated with thromboembolic events in SLE patients with LAC, we measured plasma levels of thrombomodulin (TM), von Willebrand factor (vWf), sP-selectin, vascular cell adhesion molecule-1 (sVCAM-1) and ED1-fibronectin in a study of 76 patients with SLE. Patients were subdivided on the basis of: no history of thrombosis and LAC-negative (n = 22) or LAC-positive (n = 17); positive history of thrombosis and LAC-negative (n = 16) or LAC-positive (n = 21). The median SLE disease activity index (SLEDAI) was 4. Although concentrations of sTM, vWf, sP-selectin and sVCAM-1 were significantly elevated in SLE compared with values in healthy controls, they did not differ between the four groups, between patients with or without history of thrombosis, and between patients with or without LAC. Presence of anticardiolipin antibodies could not explain these negative findings. Adjustment of the concentrations for significantly associated variables, such as age, hypertension, smoking, immunosuppressive treatment and concentrations of creatinine, cholesterol and homocysteine, did not change the main results of the study. Only sTM was significantly lower in patients with both LAC and thrombosis than in patients without both these features after adjustment for serum creatinine concentrations. In conclusion, we did not find an association between endothelial cell activation and presence of LAC or history of thrombosis in SLE.
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PMID:Lupus anticoagulant and history of thrombosis are not associated with persistent endothelial cell activation in systemic lupus erythematosus. 1147 38

The acute spinal cord infarction is a rare cause of acute-onset paraplegia. Furthermore, it is specially uncommon that the infarction occurs in patients with apparent low predisposition to vascular disease. The 20210A allele of the prothrombin gene (causing a threefold-increased risk in venous thromboembolism) was recently associated with unexplained spinal cord infarction in young women under treatment with estrogens (contraceptive pill). We report a case of anterior spinal artery syndrome resulting from an ischaemic infarction at the anterior aspect of the spinal cord in a healthy 50-year-old woman, carrying this mutation, being the first published case under treatment with transdermal estradiol. She referred the typical sudden-onset back pain associated to clinical anterior spinal artery syndrome with sphincter dysfunction and nontraumatic paraplegia. A possible multiple sclerosis was ruled out and the steroids or immunoglobulin therapy induced no clinical improvement. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord infarction from T10 to T11, with increased signal in T2-weighted image (T2). Because she referred a previous thrombophlebitis and suffered a deep-vein thrombosis one month after paraplegia, a complete coagulation study was performed. Antithrombin, proteins C and S, homocysteine, factor V Leiden, lupus anticoagulant and anticardiolipin antibodies were all normal or negatives. In opposite, the 20210A variation was positive (heterozygous) and the factor VIIIc level was very high (280 U/dl eight months later). We argue the relative importance of both findings. The patient had no a substantial recovery over a period of 20 months.Certainly, the prothrombin 20210A seems to be associated with unexplained ischemic myelopathy among the young women with estrogens.
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PMID:[Spinal cord infarction and recurrent venous thrombosis in association with estrogens and the 20210A allele of the prothrombin gene]. 1174 25

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is considered as one of the major manifestations of the disease. Epilepsy has been documented in about 10% of patients with systemic lupus erythematosus (SLE). It is well known that vascular damage in SLE occurs because of multiple mechanisms including hypercoagulation. It has been recently reported that in SLE patients raised levels of homocysteine are associated with arterial thrombosis. Hyperhomocysteinaemia is a condition due to both genetic and non-genetic factors. The most common genetic defect in homocysteine metabolism is a decreased activity of a common 5,10-methylenetetrahydrofolate reductase (MTHFR) variant (677C -->T, a thermolabile form). In this paper we describe the epileptic manifestations in six out of 55 SLE patients. Seizures were the SLE onset symptom for three patients, appeared during the active disease in two cases, and occurred during a period of clinical remission in one patient. In all cases we documented the association of epilepsy with the MTHFR mutation: the homozygosity form was present in one case (16.7%), and heterozygosity in five cases (83.3%). Nevertheless, levels of homocysteine in plasma were in the normal range. Moreover, we found a decrease in the level of S protein values in one case, a high titre positivity of anticardiolipin antibodies (aCL) (IgG and IgM) in three patients and low titre positivity (IgG) in one patient, and lupus anticoagulant (LAC) positivity in four cases. In conclusion, we believe that the abnormalities of coagulation present in our patients could be related to epileptogenesis or to an alteration of the seizure threshold.
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PMID:The 677C --> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in epileptic patients affected by systemic lupus erythematosus. 1202 72


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