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 purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR = 1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57, P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were shown to be significant predictors of the occurrence of LN. Repeated analyses excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201 was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13-5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics and African-Americans with SLE. Sociodemographic, clinical and immunologic/immunogenetic factors seem to be predictive of LN occurring after the diagnosis of SLE has been made.
Lupus 2002
PMID:Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. 1200 88

Both the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) are valid and reliable measures of disease activity in systemic lupus erythematosus (SLE). However, more study of their responsiveness is needed. The purpose of this study was to compare the responsiveness of SLAM-R and SLEDAI to disease activity changes relevant to physicians and patients. Patients were evaluated monthly for up to 12 months. At each visit, the physician completed SLAM-R and SLEDAI. Patients and physicians assessed whether relevant improvement or worsening of disease activity had occurred since the previous visit. Based on repeated measurements, effect size (ES), standardized response mean (SRM), and control-standardized response mean (CSRM) were calculated for each response category, with bootstrap-based 95% confidence intervals (CIs). Seventy-six patients contributed 471 score changes. For physicians' responses, the CSRMs for SLAM-R and SLEDAI were -0.47 versus -0.42 for improvement, 0.04 versus 0.003 for no change, and 0.65 versus 0.66 for deterioration. For patients, the CSRMs for SLAM-R and SLEDAI were -0.31 versus -0.18 for improvement, -0.08 versus 0.06 for no change, and 0.48 versus 0.05 for deterioration. Only for SLAM-R did the 95% CIs exclude zero when improvement or deterioration were detected. Similar results were found for ES and SRM. Both SLAM-R and SLEDAI are responsive to changes in SLE disease activity important to physicians. Only SLAM-R is responsive to changes important to patients. These differences may result from the inclusion of subjective SLE manifestations in SLAM-R.
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PMID:Comparison of the responsiveness of lupus disease activity measures to changes in systemic lupus erythematosus activity relevant to patients and physicians. 1200 52

In patients with systemic lupus erythematosus (SLE) increased secretion of interleukin 10 (IL-10) by peripheral blood mononuclear cells (PBMC) is associated with overproduction of pathogenic autoantibodies. Herein we report the effect of immunoadsorption (IA) on the number of IL-10 secreting PBMC in patients with active SLE. Three courses of IA were performed in 9 patients with active SLE (SLAM 15,9+/-2,9). Each course consisted of 3 treatments on consecutive days. ELISPOT assay using IL-10 specific monoclonal antibodies was used to determine the number of IL- 10 secreting PBMC before and after each treatment. Eleven healthy, age and sex matched volunteers served as controls. Anti-ds-DNA autoantibodies were reduced to 67+/-14% after the treatment period. Before therapy patients showed significantly more spontaneously IL-10 secreting PBMC than controls (p<0.01). After the first course a significant reduction of the IL-10 secreting cells to normal levels was observed which paralleled the development of disease activity (p<0.01). Our results demonstrate a concomitant reduction of disease activity, anti-ds-DNA antibodies and the number of IL-10 secreting PBMC. The production of anti-ds-DNA antibodies and IL-10 are interdependent. Thus we conclude that IA is beneficial in SLE by depletion of these pathogenic antibodies which may lead to a reduced IL-10 secretion in vivo.
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PMID:Concomitant reduction of disease activity and IL-10 secreting peripheral blood mononuclear cells during immunoadsorption in patients with active systenic lupus erythematosus. 1203 Apr 38

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-18 (IL-18) and antiangiogenic factor endostatin in the serum of 52 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects were investigated. The possible association between serum levels of these proteins and SLE activity as well as correlation between the concentrations of angiogenic cytokines and the level of endostatin was also analyzed. VEGF and IL-18 were detectable in all SLE patients and healthy control group. bFGF was measurable in 71.2% of patients with SLE and 65% of healthy persons. Endostatin was detectable in 94.2% of SLE patients and 95% of normal subjects. The serum levels of endostatin and bFGF were not significantly different in SLE and healthy control (P > 0.05). The median concentration of VEGF was higher in active SLE (238.4 pg/ml) than in inactive disease (118.1 pg/ml, P < 0.05) or in control group (133.5 pg/ml, P < 0.04). The median serum level of IL-18 was higher in the SLE patients (595.2 pg/ml) than in the control group (252.7 pg/ml) (P < 0.001). The correlations between the levels of angiogenic cytokines and endostatin with clinical features, laboratory abnormalities and also with the type of treatment were analysed. We found a positive correlation between VEGF serum concentration and SLE activity according to SLAM score (p = 0.275, P < 0.05). The significant positive correlation was also found between IL-18 and endostatin (p = 0.289, P < 0.04). In contrast, the correlation between bFGF and endostatin was significantly negative (p = - 0.299, P < 0.04). In conclusion, serum levels of the angiogenic and antiangiogenic factors may play an important role in SLE pathogenesis.
Lupus 2002
PMID:Circulating angiogenesis inhibitor endostatin and positive endothelial growth regulators in patients with systemic lupus erythematosus. 1213 72

Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.
Lupus 2002
PMID:High-dose cyclophosphamide for severe systemic lupus erythematosus. 1219 80

Thrombomodulin is a transmembranous glycoprotein of endothelial cells. In vitro it is a marker of endothelial cell injury. In vivo the levels of soluble serum thrombomodulin are regarded as parameters of disease activity in vasculitides and vasculopathies. However, the mean thrombomodulin values of different studies show marked concentration differences of the control values. The purpose of this study was to further investigate these differences. We examined 60 sera of patients with systemic lupus erythematosus (SLE) and 10 of healthy controls with three commercially available thrombomodulin ELISA kits for determination of their thrombomodulin concentration and correlation to disease activity. The disease activity of the SLE patients was determined with the SLAM-score. Raised thrombomodulin values were found in 58% (test A), 55% (test B) and 61.6% (test C). The thrombomodulin values significantly correlated with the SLE disease activity independently of the ELISA kit used (correlation coefficients: r=0.84 (test A), r=0.80 (test B), and r=0.65 (test C)). In addition, the correlation coefficients between the respective thrombomodulin values of the three tests were r=0.86 (test A to B), r=0.73 (test A to C) and r=0.79 (test B to C). However, significant differences between the results of the three ELISA kits were found between the detected thrombomodulin concentrations. The mean thrombomodulin concentrations of the controls were 25.6 ng/ml (test A), 3.53 ng/ml (test B), and 2.52 ng/ml (test C). Our results reveal that the soluble thrombomodulin values of all three commercially available ELISA kits significantly correlate with the disease activity of SLE patients. However, the results show significant differences in the determined thrombomodulin concentrations. A calibration would be required of the different ELISA kits in order to permit a direct comparison of the results of these thrombomodulin ELISAs. A general reference standard would be desirable for this calibration of all thrombomodulin ELISAs. However, this general reference standard has to be adapted to the distinct test conditions of all test kits as well as including all epitopes of thrombomodulin which are recognised by the different antibodies used in the respective test kits. At present, only ELISA kits from the same manufacturer should be used during a single study including any follow-up investigations.
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PMID:Comparison of three commercially available thrombomodulin ELISA kits. 1508 35

Due to our increasing knowledge on the pathophysiological basis of autoimmunity and the development of combined medical-obstetric clinics, pregnancy is becoming common among women with systemic lupus erythematosus (SLE). However, whether lupus worsens during pregnancy continues to be a controversial issue. SLE assessment during pregnancy is sometimes difficult due to physiological changes during this period, and common tools for measuring lupus activity during pregnancy were not available until recently. Several lupus activity scales in common use have been adapted for pregnancy [systemic lupus erythematosus in pregnancy activity index (SLEPDAI), modified lupus activity measurement (m-SLAM) and lupus activity index in pregnancy (LAI-P)]. All of them take into account the influence of pregnancy on clinical manifestation and common biochemical tests. LAI-P also accounts for specific manifestations of antiphospholipid syndrome in order not to score them as due to SLE activity. LAI-P has recently been validated for use in SLE pregnancy and could be used in future studies. However, daily assessment and management of individual pregnant women with lupus still relies on the clinical skills of attending physicians.
Lupus 2004
PMID:Evaluation of systemic lupus erythematosus activity during pregnancy. 1548 2

Genetic predisposition is the main element in susceptibility to a variety of autoimmune diseases, including systemic lupus erythematosus (SLE). Epistatic interactions between susceptibility loci play a major role in the progression of autoimmunity, as our recent work, associating a common haplotype of the SLAM/CD2 receptor family with autoimmune susceptibility in specific genomic contexts, has illustrated. Furthermore, these interactions can be abrogated in the presence of appropriate modifier loci. We postulate that susceptibility to autoimmunity may be a consequence of imbalances in immune regulation that are elicited by specific combinations of common alleles at multiple, immunoregulatory loci.
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PMID:The importance of epistatic interactions in the development of autoimmunity. 1599 2

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disorder characterised by autoantibodies production. The diagnosis of disease requires evidence of 4 out of 11 clinical and/or laboratory symptoms proposed by American College of Rheumatology. For many years attention has been drawn to the problem of finding a valid and sensitive tool for measuring SLE activity and more than 60 different methods have been proposed. Unfortunately none of them has been generally accepted. Amongst the most frequently used are SLEDAI scale and its modifications, BILAG and SLAM. The systems have been validated in prospective studies, and their reproducibility, validity and sensitivity have been compared. At present they are widely used in clinical practice. In this review currently accepted methods of SLE activity evaluation are presented.
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PMID:[Diagnostic problems and evaluation of disease activity in systemic lupus erythematosus]. 1633 36

The objective of this study was to examine factors predictive of a decline to low levels of disease activity in a cohort of systemic lupus erythematosus (SLE) patients. Patients with SLE of Hispanic (from Texas or Puerto Rico), African-American or Caucasian ethnicity from a multiethnic cohort were included. A decline to low levels of disease activity was defined as a score < or =5 as per the Systemic Lupus Activity Measure-Revised (SLAM-R) at any annual study visit if preceded by a SLAM-R > or =8. Using Generalized Estimating Equation (GEE), socioeconomic-demographic, behavioral, function, psychological, laboratory and clinical data [disease manifestations, number of ACR criteria accrued at diagnosis and damage accrual as per the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI)] from the visit preceding that meeting the definition were examined as predictors of decline to low levels of disease activity. Two-hundred and eighty-seven patients (67 Hispanics from Texas, 32 Hispanics form Puerto Rico, 120 African-Americans and 68 Caucasians), accounting for 632 visits were analyzed. In the GEE multivariable analysis, higher degrees of social support (OR = 1.208, 95% CI 1.059-1.379; P = 0.005) were predictive of a decline to low levels of disease activity, while the number of ACR criteria accrued at diagnosis (OR = 0.765, 95% CI 0.631-0.927; P = 0.006) and damage (OR = 0.850, 95% CI 0.743-0.972, P = 0.018) were negatively associated. These data suggest that a decline to low levels of disease activity in lupus patients seems to be multifactorial; this study also underscores the importance of social support for lupus patients.
Lupus 2006
PMID:Systemic lupus erythematosus in a multiethnic U.S. cohort (LUMINA) XXVII: factors predictive of a decline to low levels of disease activity. 1648 40


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