Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Our objective was to measure the relative proportions of messenger RNAs coding for soluble and membrane-bound Fas in peripheral blood mononuclear cells (PBMCs) and to quantify lymphocyte apoptosis in vitro in systemic lupus erythematosus (SLE). A RT-PCR (soluble/membrane Fas mRNA) ratio was calculated in 16 SLE, 11 RA and 16 healthy subjects' PBMCs. Apoptosis was quantitated in vitro using nick-end labeling and flow-cytometry analysis immediately and after overnight T cell activation. The mean soluble/membrane Fas ratio was 1.219+/-0.424 in the SLE group, significantly higher than in healthy subjects, 0.516+/-0.180 (P = 0.0001). There was no significant difference between inactive and active SLE groups whereas Fas ratio was higher in SLE patients with nephritis (1.460+/-0.365) compared to those without nephritis (1.031+/-0.380) (P=0.039). Mean soluble/ membrane Fas ratio in RA patients (0.975 +/- 0.37) was higher than in healthy subjects (P = 0.0003) and lower than lupus nephritis patients (P=0.015). A significantly higher proportion of mononuclear cells engaged apoptosis after T cell activation in active lupus patients, compared to control subjects. In comparison with healthy subjects, Fas alternative splicing was skewed toward the soluble form of Fas in SLE and RA. Apoptosis after T cell activation in vitro was increased in active SLE patients.
Lupus 1998
PMID:Apoptosis and expression of soluble Fas mRNA in systemic lupus erythematosus. 979 47

The role of CD4 molecules in the autoimmune and lymphoproliferative syndrome caused by murine Fas mutations was studied using the novel systemic lupus erythematosus (SLE) model, MRL-Fas(lpr(cg))/Fas(lprcg) (MRL-lpr(cg)) mice, in combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead of membrane-bound CD4 (mCD4). For this purpose, various autoimmune manifestations were compared among MRL-lpr(cg) mice homozygous (CD4slprcg), heterozygous (CD4s/mlpr(cg)), and wild-type (CD4mlpr(cg)) for the CD4 mutation. The mortality, glomerulonephritis, proteinuria, and lymphadenopathy were significantly ameliorated in CD4slprcg compared with CD4mlpr(cg) and CD4s/mlpr(cg) mice, both being comparable in these clinical characteristics. In parallel with the clinical improvement, the serum levels of immunoglobulin, anti-DNA antibodies, anti-nuclear antibodies and immune complexes, and the extent of glomerular immune deposition, were significantly lower in the former. The results indicate that mCD4 is important and can not be replaced by sCD4 in full development of SLE-like manifestations, and suggest that CD4+ T cells may aggravate the autoimmune disease by stimulating autoreactive B cells to produce autoantibodies through their helper activity in Fas mutant models. The sCD4 levels in the serum and spleen elevated with the increased accumulation of B220+CD4-CD8- (double-negative (DN)) T cells in CD4slpr(cg) mice. This, together with the significantly milder lymphadenopathy associated with lower DN T cell contents in CD4slpr(cg) than CD4mlpr(cg) mice, implies that some of abnormal DN T cells may be derived from cells of the CD4 lineage.
...
PMID:A pivotal role of cell-bound but not soluble CD4 molecules in full development of lupus-like manifestations in MRL-Fas(lprcg)/Fas(lprcg) mice. 1101 28

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule primarily involved in cell-cell adhesive interactions of the immune system. It is a cytokine-induced glycoprotein involved in the recruitment of cells into tissues undergoing inflammatory responses. The levels of soluble ICAM-1 were measured in sera of patients with systemic lupus erythematosus (SLE) using sandwich enzyme-linked immunoassay. Serum levels (mean +/- SD) of soluble ICAM-1 (sICAM-1) were significantly higher in 24 patients with SLE than in 20 controls (372+/-42 ng/dL vs 231+/-29 ng/dL, P < 0.001). A statistically significant positive correlation was observed between sICAM-1 levels and SLE disease activity index (SLEDAI) score in SLE patients, and no correlation was found between sICAM-1 and CRP, SLEDAI and CRP, or SLEDAI and ESR in patient groups (P>0.05). These findings suggest that sICAM-1 measurement may serve as an additional serologic marker of disease activity in patients with SLE.
...
PMID:Correlation of serum levels of soluble intercellular adhesion molecule-1 with disease activity in systemic lupus erythematosus. 1184 70

Antiphospholipid antibodies interact with phospholipid membranes via lipid binding plasma proteins, mostly, prothrombin and beta(2)-glycoprotein I. Using ellipsometry, we characterized prothrombin-mediated binding of lupus anticoagulant (LA) positive IgG, isolated from patients with antiphospholipid syndrome, to phosphatidylserine (PS)-containing membranes. LA IgG did not bind to membranes in the absence of prothrombin, but addition of prothrombin resulted in high-affinity binding of prothrombin-LA IgG complexes; half-maximal binding was attained at IgG and prothrombin concentrations of 10 microg/mL and 4 nM, respectively. Adsorption to membranes containing 10-40 mol % PS revealed that membrane-bound rather than solution-phase prothrombin determines the adsorption kinetics. Depletion of prothrombin and LA IgG from the solution results in rapid desorption which is strongly inhibited by addition of prothrombin but not of LA IgG. Prothrombin-mediated adsorption of monovalent Fab1 fragments prepared from patient LA IgG was negligible, indicating that monovalent interaction between prothrombin and LA IgG is weak. The kinetics of adsorption and desorption indicate that divalent binding of LA IgG to prothrombin at the lipid membrane occurs.
...
PMID:Kinetics of prothrombin-mediated binding of lupus anticoagulant antibodies to phosphatidylserine-containing phospholipid membranes: an ellipsometric study. 1245 Apr 2

Activated T cells in spontaneous lupus presumably bypass normal tolerance mechanisms in the periphery, since thymic tolerance appears intact. To determine whether such T cells indeed avoid in vivo peripheral tolerance mechanisms, we assessed their activation and recall responses after in vivo Ag stimulation in the absence of exogenously supplied costimulatory signals. Naive CD4(+) AND (transgenic mice bearing rearranged TCR specific for pigeon cytochrome c, peptides 88-104) TCR-transgenic T cells, specific for pigeon cytochrome c, from lupus-prone Fas-intact MRL/Mp+(Fas-lpr) and from H-2(k)-matched control CBA/CaJ and B10.BR mice (MRL.AND, CBA.AND, and B10.AND, respectively) were adoptively transferred into (MRL x CBA)F(1) or (MRL x B10)F(1) recipients transgenically expressing membrane-bound pigeon cytochrome c as a self-Ag. MRL.AND and control CBA.AND and B10.AND-transgenic T cells were activated and divided after transfer, indicating encounter with their cognate Ag; however, T cells from CBA.AND and B10.AND mice were impaired in their ability to proliferate and produce IL-2 after challenge with pigeon cytochrome c in ex vivo recall assays, a typical phenotype of anergized cells. By contrast, MRL.AND T cells proliferated more, and a significantly higher percentage of such cells produced IL-2, compared with control T cells. This observation that MRL T cells avoided anergy induction in vivo was confirmed in an in vitro system where the cells were stimulated with an anti-CD3 in the absence of a costimulatory signal. These experiments provide direct evidence that CD4(+) T cells from Fas-intact lupus-prone MRL mice are more resistant than nonautoimmune control cells to anergy induction. Anergy avoidance in the periphery might contribute to the characteristic finding in lupus of inappropriate T cell activation in response to ubiquitous self-Ags.
...
PMID:CD4+ T cells from lupus-prone mice avoid antigen-specific tolerance induction in vivo. 1251 36

Peripheral T cell apoptosis is upregulated in active SLE, in parallel with high expression of both membrane-bound and soluble (s) Fas. Previous studies postulated that sFas down-regulates apoptosis in vitro through its blockade of the Fas-L of cytotoxic cells. We have investigated the extent of apoptosis and sFas levels in 14 patients with active (group A) and 11 with inactive SLE (group B). Fas was predominantly expressed by CD3+ cells from group A, whose increased serological levels of sFas were linearly correlated with the TUNEL positive cell population, whereas low titers paralleled a mild level of apoptosis in group B. This association was also investigated by measuring the effect of sFas on both cell proliferation and caspase activation. We found that incubation with sFas greatly suppressed proliferation of CD3+ cells, especially in group B, and in control cells from healthy donors whose content of CPP32 active products was significantly increased. We postulate that sFas promotes a pro-apoptogen effect, which would explain the high susceptibility to apoptosis in active lupus, and that the apoptosis program itself includes release of sFas to spread the death signal.
Lupus 2003
PMID:Enhancement of T cell apoptosis correlates with increased serum levels of soluble Fas (CD95/Apo-1) in active lupus. 1258 20

A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) was recently found and shown to possess a downregulatory function as a membrane-bound CTLA-4 molecule. The purpose of the study was to investigate the expression of sCTLA-4 molecule in patients with systemic lupus erythematosus (SLE). One hundred patients with SLE and 40 age- and sex-matched healthy individuals were enrolled in the study. The results showed that patients with SLE have significantly higher levels of sCTLA-4 in sera than healthy controls (21.6 +/- 12.3 ng/ml versus 5.9 +/- 5.4 ng/ml, P < 0.001). Increased expression of sCTLA-4 mRNA in peripheral blood mononuclear cells (PBMCs) was also found in SLE patients. However, we could not find a statistically significant correlation between the serum levels of sCTLA-4 and lupus disease activities. The reported CTLA-4 gene polymorphism in promoter region at position -318 did not affect the levels of sCTLA-4. To the best of our knowledge, this is the first report showing that patients with SLE have increased sCTLA-4 expression. However, the mechanism and role of increased sCTLA-4 in the pathogenesis of SLE remains elucidated.
...
PMID:Increased expression of soluble cytotoxic T-lymphocyte-associated antigen-4 molecule in patients with systemic lupus erythematosus. 1279 Oct 95

The complement system is comprised of a number of serum and membrane-bound proteins that play an important role in the elimination of foreign microorganisms while protecting the host organism from complement-related damage. Complement has also been shown to participate in the generation of normal humoral immune responses to foreign antigens. Recent studies suggest that the functions of complement may be extended to include the maintenance of B cell tolerance. Complement receptor 2 (CR2/CD21) has been implicated in lupus susceptibility in both humans and animal models of disease. Located primarily on B cells and follicular dendritic cells, CR2 binds C3 degradation products that have become covalently bound to antigen or immune complexes in the process of complement activation. The mechanism by which CR2 might regulate B cell reactivity to autoantigens has not been elucidated, but may involve direct effects on B cell tolerance or indirect effects on T cell tolerance.
...
PMID:Complement and autoimmunity. 1449 71

Various therapeutic strategies have been developed to tolerize autoreactive T cells and prevent autoimmune pathology in type 1 diabetes. 4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. The administration of an agonistic anti-4-1BB antibody (2A) dramatically reduced the incidence and severity of experimental autoimmune encephalomyelitis (EAE). Treatment with the same antibody in Fas-deficient MRL/lpr mice blocked lymphadenopathy and lupus-like autoimmune processes. Paradoxically, transgenic non-obese diabetic (NOD) mice overexpressing membrane-bound agonistic single-chain anti-4-1BB Fv in pancreatic beta cells developed more severe diabetes than their non-transgenic littermates, with earlier onset, faster diabetic processes, and higher mortality. Forty percent of transgenic mice developed diabetes by 4 weeks of age, compared with their control littermates, which first exhibited diabetes at 14 weeks. The frequency of diabetes in female transgenics reached 70% by 8 weeks of age. Most female transgenic mice died around 12 weeks. Consistent with this, transgenic mice developed earlier and more severe insulitis and showed stronger GAD-specific T-cell responses, compared with age-matched control littermates. Our results indicate an adverse effect of transgenic anti-4-1BB scFv in NOD mice and suggest a potential risk of this anti-4-1BB-based immunotherapy for autoimmune diseases.
...
PMID:Anti-4-1BB-based immunotherapy for autoimmune diabetes: lessons from a transgenic non-obese diabetic (NOD) model. 1459 49

Endothelial microparticles (EMP) are small vesicles released from disturbed endothelial cells (EC). Owing to the central importance of EC injury in thrombotic and inflammatory conditions, assay of EMP as a marker of EC disturbance has come under intensive development by several laboratories. The review begins with established markers of EC injury, commonly soluble markers such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, von Willebrand factor (vWF), etc., pointing out that many of these are in fact mixtures of true soluble molecules with membrane-bound forms, for example, EMP. Assays of EMP from different labs are reviewed and standardization of assay is recommended. EMP are heterogeneous: those released in activation vs. apoptosis are distinctive in phenotypic markers and procoagulant properties. Application of EMP phenotype analysis can distinguish EC state of activation from apoptosis. Some EMP carry functional vWF with properties different from soluble vWF. Certain EMP bind to and activate monocytes; EMP-monocyte conjugates were found to be a marker of inflammatory disease such as multiple sclerosis (MS), and to enhance transendothelial migration of leukocytes in vitro. Clinical studies have revealed elevated plasma levels of EMP in lupus anticoagulant (LA), multiple sclerosis (MS), thrombotic thrombocytopenic purpura (TTP), coronary artery disease (CAD), hypertension, preeclampsia, and diabetes. Further refinement of EMP assay could open new windows for evaluating and monitoring endothelial injury in thrombotic and inflammatory disorders.
...
PMID:Endothelial microparticles as markers of endothelial dysfunction. 1497 33


<< Previous 1 2 3 4 5 6 7 8 Next >>

---