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)

Patients with systemic lupus erythematosus (SLE) have increased percentages of activated T cells and increased numbers of cells with mutations in their hypoxanthineguanine phosphoribosyltransferase (hprt) gene, as judged by growth in the presence of 6-thioguanine. To study the relevance of these mutant T cells to disease pathogenesis, we have assessed the phenotype and functional capabilities of such cells from 21 patients with SLE who never had received cytotoxic drugs. The frequency of T cells with mutations in hprt in the blood of these patients ranged from normal to 25 times normal (mean +/- SEM [21.1 +/- 6.1] x 10(-6) versus [4.8 +/- 0.8] x 10(-6), in 15 age-matched normal individuals, P < 0.001) and correlated significantly with disease duration. CD4+ and CD8+ phenotypes were comparable among mutated and nonmutated clones from both patients and normals. Although the frequency of CD3+CD4-CD8- cells was low, it was increased among SLE-derived T cells (mutated and wild-type) compared with clones derived from normals (5% for SLE vs 1% for normals). A substantial percentage of all clones were able to help autologous B cells to produce anti-ssDNA, 11 of 68 (16%) selected clones and 3 of 28 (11%) nonselected clones. Help for autoantibody production was confined to CD4+ SLE-derived T cell clones. It could be blocked using an anti-HLA-DR mAb, suggesting that classical cognate help was operative. This represents the first estimate of the frequency of T cells able to drive autoantibody production in SLE.
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PMID:Characterization of in vivo mutated T cell clones from patients with systemic lupus erythematosus. 782 67

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell-cell adhesive interactions of the immune system. The levels of soluble ICAM-1 (s-ICAM-1) shed into the circulation were studied in the sera of patients with systemic lupus erythematosus (SLE) by an enzyme linked immunosorbent assay. Serum concentrations of s-ICAM-1 were significantly increased in 61 patients with SLE compared to 51 controls (mean +/- SEM: 564 +/- 30 versus 348 +/- 17 ng/ml, p < 0.0001) and 41% of patients had higher serum levels than the normal cut off value of 584 ng/ml. Among the various clinical manifestations, skin involvement was significantly associated with high serum levels of s-ICAM-1. Individual values of serum s-ICAM-1 concentrations in patients with SLE correlated significantly with two different disease activity indices, as well as with the erythrocyte sedimentation rate and serum levels of soluble interleukin-2 receptors, but not with serum levels of anti-dsDNA antibodies or C4. No significant differences in s-ICAM-1 levels were found between patients receiving immunomodulatory treatment and those who were not. These findings suggest that s-ICAM-1 measurement may serve as an additional serologic marker of disease activity in patients with SLE. Further studies to determine whether increased s-ICAM-1 shedding has any pathogenetic significance or biological role in SLE are warranted.
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PMID:Increased levels of intercellular adhesion molecule-1 in the serum of patients with systemic lupus erythematosus. 790 80

In view of recent data demonstrating increased expression of intercellular adhesion molecule-1 (ICAM-1) in the skin of patients with systemic sclerosis (SSc) we studied whether levels of soluble ICAM-1 (s-ICAM-1) shed into the circulation are increased in patients with this disorder. We also compared blood levels of s-ICAM-1 in SSc with those in systemic lupus erythematosus (SLE) and we investigated any possible association of s-ICAM-1 with soluble IL-2 receptor (s-IL 2R) levels, the latter being considered as a marker of lymphocyte activation. Patients with SSc had increased levels of sICAM-1 compared with healthy control subjects (mean +/- SEM, 587 +/- 34 versus 373 +/- 27 ng/ml, P < 0.0001). Patients with diffuse rapidly progressive disease had the highest s-ICAM-1 levels. No association was observed between the extent of skin or internal organ involvement and s-ICAM-1 levels. Patients with digital ulcers had significantly elevated s-ICAM-1, but not s-IL 2R, levels. No correlation was detected between individual s-ICAM-1 and S-IL 2R levels in SSc patients. These novel findings suggest that circulating s-ICAM-1 levels may be a useful marker of endothelial activation in SSc; however, further studies are needed to determine the role of ICAM-1 in the pathogenesis of this disorder.
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PMID:Circulating intercellular adhesion molecule-1 in patients with systemic sclerosis. 809 61

Cytokines are important protein mediators in inflammatory joint diseases. The synovial fluid and plasma concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IF-alpha) and interferon-gamma (IF-gamma) were measured by RIA and ELISA in 28 rheumatoid arthritis (RA) patients (5 males and 23 females). Ten patients with knee effusions due to other causes (osteoarthritis, psoriasis, gout, rheumatic fever, systemic lupus erythematosus) were also studied. Eight of the RA patients had erosive disease. The synovial fluid IL-1 alpha and IL-2 concentrations were higher in Group 1 (erosive) [IL-1 alpha: 524 pg/ml (SEM: 127), IL-2: 3.28 ng/ml (SEM: 1.0)] than in either Group 2 (non-erosive) [IL-1 alpha: 241 pg/ml (SEM: 24), IL-2: 1.93 ng/ml (SEM: 0.6)] or Group 3 (non-RA) [IL-1 alpha: 267 pg/ml (SEM: 58), IL-2: 0.35 ng/ml (SEM: 0.6)] (p < 0.003 and p < 0.06 respectively). Plasma IL-1 and IL-2 levels were higher in Group 1 [IL-1 alpha: 408 pg/ml (SEM: 107), IL-2: 4.20 ng/ml (SEM: 1.5)] than in Group 2 [IL-1 alpha 150 pg/ml (SEM: 15), IL-2: 2.58 ng/ml (SEM: 0.7)] or Group 3 [IL-1 alpha: 140 pg/ml (SEM: 11), IL-2: 1.93 ng/ml (SEM: 0.3)] (p < 0.01, p < 0.009 respectively). There were no differences in the IFN-alpha, IFN-gamma or TNF-alpha levels between groups. These findings suggest that plasma cytokines levels may reflect synovial levels and that IL-1 alpha may play a significant role in erosive joint disease.
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PMID:Cytokine concentrations in the synovial fluid and plasma of rheumatoid arthritis patients: correlation with bony erosions. 816 43

The level of von Willebrand factor antigen (vWF) released by endothelial cells in response to IgG isolated from 18 patients with systemic lupus erythematosus (SLE), eight patients with the anti-phospholipid syndrome (APS) and 22 controls has been measured. Incubation with IgG from the combined patient group resulted in a significantly greater release of vWF (mean stimulation index +/- SEM, 4.57 +/- 0.78) when compared with controls (1.96 +/- 0.22, P = 0.003). Furthermore, IgG from 17 patients who had had a history of thrombosis induced higher levels of vWF release (5.33 +/- 1.09) when compared with the controls (P = 0.008). These findings suggest that IgG from patients with SLE or APS is capable of stimulating vWF release and that this ability may be implicated in the thrombotic events that are observed in these conditions.
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PMID:Stimulation of von Willebrand factor antigen release by immunoglobulin from thrombosis prone patients with systemic lupus erythematosus and the anti-phospholipid syndrome. 842 24

Lupus anticoagulants (LA) are associated with an increased risk of thrombosis and laboratory detection is of major importance. Various tests are available for LA screening and confirmation, but they differ in sensitivity and specificity, frequently lacking the ability to discriminate between the presence of LA, heparin and oral anticoagulants. We noticed that a patient with LA who had a prolonged activated partial thromboplastin time (APTT) by our routine method, gave a normal result with a different APTT reagent. This latter reagent, which contained soy bean phosphatides (SBP), was compared with a reagent containing rabbit brain phospholipids complexed with kaolin (RBK), for APTT measurement in a variety of patients. There was no significant difference in APTT ratio between the two reagents in plasma samples from healthy normal subjects. In LA samples, SBP gave consistently lower APTT ratios than RBK (mean +/- SEM, 1.04 +/- 0.05 and 2.08 +/- 0.19 for SBP and RBK respectively; P < 0.001). In LA patients receiving oral anticoagulants for antithrombotic prophylaxis or treatment, the APTT ratio was again significantly shorter with SBP (1.60 +/- 0.17 and 3.40 +/- 0.67; P < 0.05). In LA negative patients receiving oral anticoagulants, the relationship was reversed, and a higher APTT ratio was obtained with SBP than RBK (1.61 +/- 0.13 and 1.31 +/- 0.12; P < 0.001). In addition, there were no significant differences in APTT ratios for the two reagents when samples from patients receiving heparin therapy, or patients with acquired factor VIII deficiency or inherited deficiency of factor VIII or IX were studied. The use of the SBP reagent alongside a LA sensitive APTT reagent allows a rapid screening for LA, as well as a confirmation of the phospholipid dependency of the inhibitor.
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PMID:A rapid screen for lupus anticoagulant with good discrimination from oral anticoagulants, congenital factor deficiency and heparin, is provided by comparing a sensitive and an insensitive APTT reagent. 916 15

MRL/MpJ-Fas(lpr) (Fas(lpr)) mice develop a rapidly fatal form of systemic autoimmune disease characterized by glomerulonephritis and vasculitis similar to severe cases of systemic lupus erythematosus in humans. To evaluate the requirement for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of tissue injury in this model, we created ICAM-1-deficient MRL/MpJ-Fas(lpr) (ICAM-1/Fas(lpr)) mice. ICAM-1 deficiency resulted in a striking improvement in the survival of Fas(lpr) mice (median +/- SEM survival of Fas(lpr) = 26 +/- 1.7 vs ICAM-1/Fas(lpr) = 47 +/- 2.4 wk, p < 0.0001) and the increased survival was associated with delayed elevations of blood urea nitrogen levels in the ICAM-1/Fas(lpr) mice. Histologic examination of the ICAM-1/Fas(lpr) mice revealed an overall reduction in glomerular disease and a significant reduction in vasculitis in the kidney, lung, skin, and salivary glands when compared with Fas(lpr). These findings indicate that ICAM-1 plays a major role in development of glomerular and vascular injury in Fas(lpr) mice.
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PMID:Intercellular adhesion molecule-1 deficiency protects MRL/MpJ-Fas(lpr) mice from early lethality. 925 74

Pulmonary renal syndrome (PRS), defined as a combination of diffuse pulmonary hemorrhage and glomerulonephritis (GN), represents a severe syndrome for which minimal outcome data are available in the literature. We present a retrospective study of 14 consecutive patients from 1996 to 2000. Mean patient age was 65 +/- 2.1 (SEM) years, and 7 patients were women. At presentation, Po(2) on air was 6.0 +/- 0.5 kPa, and creatinine level was 554 +/- 70 micromol/L. Thirteen patients had systemic vasculitis, and 1 patient had systemic lupus erythematosus (SLE). Five patients were cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) positive, and 7 patients were perinuclear ANCA (P-ANCA) positive; 2 of the latter patients also were positive for anti-glomerular basement membrane antibodies. Renal biopsy was performed in 10 patients. Histological examination showed membranous GN in the patient with SLE and segmental necrotizing crescentic GN in the other 9 patients examined. Twelve of 14 patients were initially dialysis dependent, and 8 of 14 patients required ventilatory support. All patients were treated with corticosteroids, 8 of 14 patients were administered intravenous methylprednisolone, 13 of 14 patients were administered daily cyclophosphamide, and 12 of 14 patients underwent plasma exchange. Patients were followed up for 22 +/- 9 months. Early reduction in cyclophosphamide dosage was required in 9 patients for neutropenia. Seven patients were alive at the end of follow-up, but 5 patients (36%) died in the first month. Of the survivors, 85% and 67% were alive after 1 and 2 years of completed follow-up: 83% and 75% of these survivors were dialysis independent, respectively. Five relapses were seen in 4 patients. One patient died of progressive pulmonary fibrosis. Sepsis was a major factor in 6 of 7 deaths. This patient group was older than those previously reported. Findings confirm previous suggestions that PRS requiring intensive care treatment has high mortality, and early survivors have good 1- and 2-year outcomes. Cyclophosphamide-associated neutropenia and infection were frequent contributors to death, and less toxic alternatives may improve outcome in PRS.
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PMID:Pulmonary renal syndrome: a 4-year, single-center experience. 1177

Women with systemic lupus erythematosus (SLE) are at risk for premature atherothrombosis independent of Framingham risk factors. We investigated whether endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes to circulating tissue factor (TF) levels in this disease. Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation were determined in women with SLE, healthy control subjects, and subjects with coronary artery disease (CAD) (n = 43/group). Quantification of circulating apoptotic ECs was performed by flow cytometry (CD146(+) cells that stained for Annexin V [CD146(AnnV+)]) and immunofluorescent microscopy. Plasma TF was measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy control and CAD subjects, patients with SLE had higher numbers of circulating CD146(AnnV+) cells (10 +/- 3, 18 +/- 5, and 89 +/- 32 cells/mL, respectively, mean +/- SEM; P <.01). Increased CD146(AnnV+) cells correlated strongly with abnormal vascular function (P =.037). After adjusting for known predictors of endothelial function, CD146(AnnV+) was the only variable that predicted FMD (beta = -4.5, P <.001). Increased CD146(AnnV+) was strongly associated with elevated levels of circulating TF (r =.46, P =.002). Circulating apoptotic ECs are elevated in young women with SLE and strongly correlate with markedly abnormal vascular function and elevated TF levels. Heightened endothelial apoptosis may represent an important mechanism for development of atherothrombosis in SLE.
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PMID:Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. 1472 73

The aim of this study was to analyze the renal outcome of pediatric lupus nephritis in the past two decades. We retrospectively reviewed the medical records of patients who fulfilled the 1987 American Rheumatism Association revised criteria for systemic lupus erythematosus who were followed up at the National Taiwan University Hospital between 1980 and 2001. All new patients who were under 18 years of age at the time of diagnosis were enrolled and were followed up until death, loss to follow-up, or till the end of 2002. The response to the treatment and renal outcome were analyzed. Seventy-two children (64 girls and 8 boys) were enrolled in the study. The mean age at diagnosis was 13.93+/-0.35 years (mean +/- SEM). The mean duration of follow-up was 7.12+/-0.51 years. The 5-year renal survival rate (survival without dialysis or transplantation) was 63.13% and the 10-year survival rate was 53.54%. It was significantly better in patients receiving cyclophosphamide (CYC) pulse therapy. The 5-year survival rate for these patients was 87.82% and the 10-year survival rate was 81.06%. The renal survival curve was better in the CYC pulse therapy group than in the no CYC pulse therapy group, with p=0.0022. The duration between the diagnosis of lupus nephritis and end-stage renal disease (ESRD) was significantly longer in the CYC group (9.66+/-1.32 yrs) than in the no CYC group (3.24+/-0.94 yers), p=0.036. In the multivariate analysis, risk factors of developing ESRD were failure to achieve complete remission, higher serum creatinine at the initiation of treatment, and not receiving CYC pulse therapy. The renal survival was significantly better in the CYC pulse therapy group. The CYC pulse therapy was recommended in pediatric lupus nephritis patients and every effort should be made to achieve complete remission.
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PMID:Retrospective analysis of the renal outcome of pediatric lupus nephritis. 1529 92


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