Diagnosis and early detection of CNS-SLE in MRL/lpr mice using peptide microarrays (GPL14921)
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ABSTRACT:
ORGANISM(S): synthetic construct Mus musculus
PROVIDER: GSE57388 | GEO | 2014/05/08
SECONDARY ACCESSION(S): PRJNA246380
REPOSITORIES: GEO
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Project description:We investigated whether mouse serum autoantibody binding patterns on random-sequence peptide microarrays (immunosignaturing) can be used for diagnosing and predicting the onset of lupus and its central nervous system (CNS) manifestations. Submitter states "We have no processed data to submit. We have no gpr files to submit." To identify possible predictive and diagnostic peptides of lupus and CNS-lupus, we carried out two studies and selected peptides in common across both studies. In the first study we tested 3-6 MRL/lpr, MRL/mp and C3H/HeJ mice at four months of age. For study two we tested 9-10 MRL/lpr and MRL/mp at 1.5 and 4 months of age. In both studies the mice sera were diluted 1/500 and analyzed using microarray peptides from platform GPL14921. We ran each sample in triplicate. The MRL/lpr and MRL/mp are the autoimmune strains and the C3H/HeJ is the control strain.
2014-05-08 | E-GEOD-57388 | biostudies-arrayexpress
Project description:In addition to determining possible diagnostic and predictive peptides of lupus and CNS-lupus, we also used our microarray technology along with the Guitope computer program to determine possible natural protein match to five monoclonal autoantibodies that were created using one of the autoimmune MRL/lpr mouse. Submitter states "We have no processed data to submit. We have no gpr files to submit."
2014-05-08 | GSE57389 | GEO
Project description:In addition to determining possible diagnostic and predictive peptides of lupus and CNS-lupus, we also used our microarray technology along with the Guitope computer program to determine possible natural protein match to five monoclonal autoantibodies that were created using one of the autoimmune MRL/lpr mouse. Submitter states "We have no processed data to submit. We have no gpr files to submit." Microarray analysis was performed on five monoclonal brain-reactive autoantibodies (F9, G10, G4, D1 and D9) that were created from one autoimmune mouse with altered behavior. These samples were tested in duplicated along with a control sample on the GPL17600 platform.
2014-05-08 | E-GEOD-57389 | biostudies-arrayexpress
Project description:BackgroundAn accurate method that can diagnose and predict lupus and its neuropsychiatric manifestations is essential since currently there are no reliable methods. Autoantibodies to a varied panel of antigens in the body are characteristic of lupus. In this study we investigated whether serum autoantibody binding patterns on random-sequence peptide microarrays (immunosignaturing) can be used for diagnosing and predicting the onset of lupus and its central nervous system (CNS) manifestations. We also tested the techniques for identifying potentially pathogenic autoantibodies in CNS-Lupus. We used the well-characterized MRL/lpr lupus animal model in two studies as a first step to develop and evaluate future studies in humans.ResultsIn study one we identified possible diagnostic peptides for both lupus and altered behavior in the forced swim test. When comparing the results of study one to that of study two (carried out in a similar manner), we further identified potential peptides that may be diagnostic and predictive of both lupus and altered behavior in the forced swim test. We also characterized five potentially pathogenic brain-reactive autoantibodies, as well as suggested possible brain targets.ConclusionsThese results indicate that immunosignaturing could predict and diagnose lupus and its CNS manifestations. It can also be used to characterize pathogenic autoantibodies, which may help to better understand the underlying mechanisms of CNS-Lupus.
| S-EPMC4065311 | biostudies-literature
Project description:BackgroundLupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus. Anti-double-stranded (ds) DNA immunoglobulin G (IgG) plays a pivotal role in the pathogenesis of LN. Currently, there are various therapies for patients with LN; however, most of them are associated with considerable side effects. We confirmed previously that ALW (ALWPPNLHAWVP), a 12-amino acid peptide, inhibited the binding of polyclonal anti-dsDNA antibodies to mesangial cells and isolated glomeruli in vitro. In this study, we further investigate whether the administration of ALW peptide decreases renal IgG deposition and relevant damage in MRL/lpr lupus-prone mice.MethodsForty female MRL/lpr mice were randomly divided into four groups. The mice were intravenously injected with D-form ALW peptide (ALW group), scrambled peptide (PLP group), and normal saline (NaCl group) or were not treated (blank group). The IgG deposition, the histopathologic changes, and the expressions of profibrotic factors were analyzed in the kidney of MRL/lpr mice.ResultsCompared with the other groups, glomerular deposition of IgG, IgG2a, IgG2b, and IgG3 was decreased in the ALW group. Moreover, ALW administration attenuated renal histopathologic changes in MRL/lpr mice, including mesangial proliferation and infiltration of inflammatory cells. Furthermore, the expressions of profibrotic cytokines, such as transforming growth factor-beta1 (TGF-?1) and platelet-derived growth factor B (PDGF-B), decreased in the serum and kidney tissue of ALW-treated mice.ConclusionsOur study demonstrated that ALW peptide ameliorates the murine model of LN, possibly through inhibiting renal IgG deposition and relevant tissue inflammation and fibrosis.
| S-EPMC6889545 | biostudies-literature
Project description:BackgroundThe roles of gut microbiota in the pathogenesis of SLE have been receiving much attention during recent years. However, it remains unknown how fecal microbiota transplantation (FMT) and microbial metabolites affect immune responses and lupus progression.MethodsWe transferred fecal microbiota from MRL/lpr (Lpr) mice and MRL/Mpj (Mpj) mice or PBS to pristane-induced lupus mice and observed disease development. We also screened gut microbiota and metabolite spectrums of pristane-induced lupus mice with FMT via 16S rRNA sequencing, metagenomic sequencing, and metabolomics, followed by correlation analysis.ResultsFMT from MRL/lpr mice promoted the pathogenesis of pristane-induced lupus and affected immune cell profiles in the intestine, particularly the plasma cells. The structure and composition of microbial communities in the gut of the FMT-Lpr mice were different from those of the FMT-Mpj mice and FMT-PBS mice. The abundances of specific microbes such as prevotella taxa were predominantly elevated in the gut microbiome of the FMT-Lpr mice, which were positively associated with functional pathways such as cyanoamino acid metabolism. Differential metabolites such as valine and L-isoleucine were identified with varied abundances among the three groups. The abundance alterations of the prevotella taxa may affect the phenotypic changes such as proteinuria levels in the pristane-induced lupus mice.ConclusionThese findings further confirm that gut microbiota play an important role in the pathogenesis of lupus. Thus, altering the gut microbiome may provide a novel way to treat lupus.
| S-EPMC10018936 | biostudies-literature
Project description:OBJECTIVE:We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus-like disease in MRL/lpr mice. METHODS:EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and messenger RNA expression data. Inhibition of EZH2 in MRL/lpr mice was achieved by intraperitoneal 3'-deazaneplanocin (DZNep) administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti-double-stranded DNA (anti-dsDNA) antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed. RESULTS:EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL/lpr mice, inhibition of EZH2 by DZNep was confirmed by significant reduction of EZH2 and H3K27me3 in splenocytes. Inhibiting EZH2 with DZNep treatment before or after disease onset improved survival and significantly reduced anti-dsDNA antibody production. DZNep-treated mice displayed a significant reduction in renal involvement, splenomegaly, and lymphadenopathy. Lymphoproliferation and numbers of double-negative T cells were significantly reduced in DZNep-treated mice. Concentrations of circulating cytokines and chemokines, including tumor necrosis factor, interferon-?, CCL2, RANTES/CCL5, interleukin-10 (IL-10), keratinocyte-derived chemokine/CXCL1, IL-12, IL-12p40, and CCL4/macrophage inflammatory protein 1?, were decreased in DZNep-treated mice. CONCLUSION:EZH2 is up-regulated in multiple cell types in lupus patients. Therapeutic inhibition of EZH2 abrogates lupus-like disease in MRL/lpr mice, suggesting that EZH2 inhibitors may be repurposed as a novel therapeutic option for lupus patients.
| S-EPMC6764871 | biostudies-literature
Project description:RNA-sequencing analysis of plasmacytoid dendritic cells isolated from lupus mice
| PRJNA284002 | ENA