Systemic lupus erythematosus is associated with enhanced CD4 + T cell metabolism and can be reversed by metabolic modulators.

Abstract Objective The premature atherosclerosis seen in patients with systemic lupus erythematosus (SLE) is not explained by traditional risk factors. SLE disease activity, such as renal involvement and presence of autoantibodies, associated elevated serum levels type I interferon (IFN‐I), a family cytokines potent antiviral antiproliferative effects. This study was undertaken to test the hypothesis that IFN‐I could lead endothelial dysfunction, surrogate for cardiovascular disease, causing...

Mice homozygous for the gene lpr develop marked lymphadenopathy and a spectrum of autoantibodies closely resembling that human systemic lupus erythematosus. The unusual T cell phenotype expanded lymphocyte population T-dependence several antibodies in this strain have suggested primary abnormalities underlie autoimmune syndrome. Using double chimeras, we now show expression B cells is absolutely necessary autoantibody production. Combinations anti-Thy 1.2 + C' treated bone marrow from...

Abstract Objective Systemic lupus erythematosus (SLE) is diagnosed according to a spectrum of clinical manifestations and autoantibodies associated with abnormal expression type I interferon (IFN‐I)–stimulated genes (ISGs). The role IFN‐I in the pathogenesis SLE remains uncertain, partly due lack suitable animal models. objective this study was examine signaling murine induced by 2,6,10,14‐tetramethylpentadecane (TMPD). Methods receptor–deficient (IFNAR −/− ) 129Sv mice wild‐type (WT)...

Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). There evidence that polymorphisms the genes of inflammatory mediators may predispose development LN SLE. In this study, we examined role functional monocyte chemoattractant protein 1 (MCP-1) polymorphism SLE LN.DNA paired urine serum samples were obtained from 134 (> or =4 American College Rheumatology criteria for SLE; 49 85 without LN) 118 controls. MCP-1 genomic...

Abstract Early systemic treatment of nonobese diabetic mice with high doses recombinant adeno-associated virus (rAAV) vector expressing murine IL-10 prevents type 1 diabetes. To determine the therapeutic parameters and immunological mechanisms underlying this observation, female at 4, 8, 12 wk age were given a single i.m. injection rAAV-murine (104, 106, 108, 109 infectious units (IU)), rAAV-vector truncated fragment (109 IU), or saline. Transduction rAAV-IL-10 IU completely prevented...

Sle3 is an NZM2410-derived lupus susceptibility locus on murine chromosome 7. Congenic recombination has resulted in a novel mouse strain, B6.Sle3, associated with serum antinuclear autoantibodies (ANAs), T cell hyperactivity, and elevated CD4/CD8 ratios. An OVA-specific TCR transgene was used as tool to demonstrate that facilitated heightened expansion vitro, vivo, following antigen challenge. Indeed, continued noted even response tolerogenic signal. However, these phenotypes did not appear...

Abstract Introduction More than half of systemic lupus erythematosus (SLE) patients show evidence excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection IFN-I proteins in serum is unreliable, the measurement interferon-stimulated gene (ISG) expression expensive time consuming. The aim this study was to identify surrogate marker for activity clinical samples monitoring response therapy. Methods Monocyte surface Fcγ...

Abstract Sle1 is a potent autoimmune susceptibility locus on chromosome 1 originally identified in genome scan of testcross progeny between the systemic lupus erythematosus-prone NZM2410 strain and C57BL/6. We subsequently produced B6.NZMc1, congenic carrying NZM2410-derived genomic interval B6 background demonstrated that mediated loss tolerance to chromatin both B T cell compartments. In this communication, we show by adoptive transfer experiments phenotypes are completely reconstituted...

Measurement of high sensitivity C-reactive protein (hs-CRP), has been used in the assessment disease activity numerous rheumatic conditions including systemic lupus erythematosus (SLE). However, utility hs-CRP measurement patients with is uncertain. This study examined if can be to assess activity, severity and cardiovascular risk SLE. Serum samples from 601 visits 213 SLE 134 controls were analysed for by nephelometry. Detailed demographic data obtained all subjects medication history key...

Abstract Introduction The high-affinity receptor for IgG Fcγ/CD64 is critical the development of lupus nephritis (LN). Cross-linking Fc on recruited monocytes by IgG-containing immune complexes a key step in immune-complex-mediated systemic erythematosus (SLE). goal this study was to determine whether expression (FcγR) I circulating associated with inflammation and renal disease SLE patients. Methods We studied 205 patients (132 LN 73 without LN) along 74 healthy control individuals. Surface...

The anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) has high sensitivity and specificity for rheumatoid arthritis (RA). However, detection of anti-CCP in patients with active pulmonary tuberculosis (TB) recently been reported. To determine whether this activity was specific the residue, anti-CCP-positive sera CCP versus that unmodified arginine-containing (CAP) examined TB compared RA.Anti-CCP anti-CAP from (n = 49), RA 36), controls 18) were tested by...

Objective. Anti-cyclic citrullinated peptide (CCP) antibodies are a serological marker for rheumatoid arthritis (RA); up to 10%–15% of patients with systemic lupus erythematosus (SLE) also positive. While anti-CCP in RA is citrulline-dependent, some other diseases citrulline-independent and reacts both CCP the unmodified (arginine-containing) cyclic arginine (CAP). We investigated citrulline dependence its significance SLE. Methods. IgG was compared by ELISA anti-CAP sera from SLE (n = 335)...

Abstract Increasing evidence suggests that type 1 IFN (IFN-αβ) is associated with pathogenesis of Th1-mediated diabetes (T1D). A major source IFN-αβ plasmacytoid dendritic cells (pDCs). In this study, we analyzed peripheral blood pDC numbers and functions in at-risk, new-onset, established T1D patients controls. We found subjects at risk for new-onset possessed significantly increased pDCs but similar number myeloid DCs when compared were not affected by age declined increasing control...

Abstract In systemic lupus erythematosus, defective clearance of apoptotic debris and activation innate cells result in a chronically activated type 1 IFN response, which can be measured PBMCs most patients. Metformin, widely used prescription drug for Type 2 diabetes, has therapeutic effect several mouse models through mechanisms involving inhibition oxidative phosphorylation decrease CD4+ T cell activation. this study, we report that from human healthy controls erythematosus patients,...

Most individuals with autoimmune and other immune disorders undergo initial evaluation in the community setting. Since misdiagnosis of systemic diseases can have serious consequences, we evaluated physicians' accuracy diagnosing consequences misdiagnosis.We studied patients referred to our Autoimmune Disease Center for 13 months (n = 476). We estimated degree agreement final diagnosis (kappa statistic) indexes (sensitivity, specificity, predictive values) referring diagnoses.We found a 49%...

Abstract Intraperitoneal injection of the hydrocarbon oil pristane into normal mice leads to a lupus-like autoimmune syndrome. Although advances in defining roles cellular and humoral mediators involved this syndrome have been made, mechanisms that initiate break tolerance leading autoimmunity remain unknown. We describe study induces apoptosis both vivo vitro. Pristane arrests cell growth death by via mitochondrial pathway caspase activation dose-dependent manner. Nuclear autoantigens...

Abstract Sle1 is a major susceptibility locus in the NZM2410 murine model of systemic lupus erythematosus. When isolated on C57BL/6 background B6.Sle1 congenic strain, results production high levels anti-chromatin IgG Abs, histone-specific T cells, and increased B cell activation. We have shown by mixed bone marrow chimeras with allotypic markers that expressed cells. Using same technique, we now show it also To assess whether intrinsic defects or bred μMT Tcrα−/− mutations onto resulting...

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects women more frequently than men. In the (NZB times NZW)F1 mouse, a murine SLE model, presence or absence of estrogen markedly influences rate progression disease. Three organochlorine pesticides with estrogenic effects were administered chronically to ovariectomized female mice, and we measured time development renal disease, principal clinical manifestation in this model. Treatment chlordecone, methoxychlor, o,p...

Mice homozygous for the lpr gene develop autoantibodies and polyclonal B cell activation similar to what is seen in human systemic lupus erythematosus patients. We have previously shown that an lpr-specific intrinsic defect was necessary autoantibody production this model. In current study, we further defined these autoantibody-producing cells. Two major subsets of cells been described. B-1 (CD5+ cells) can be distinguished from conventional on basis phenotype, cytokine secretion,...