B cell signature during inactive systemic lupus
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30153 | GEO | 2011/06/23
SECONDARY ACCESSION(S): PRJNA143913
REPOSITORIES: GEO
Similar Datasets
Project description:Systemic lupus erythematosous (SLE) is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomes of quiescent lupus patients to normal B cell transcriptomes. 17 patients with quiescent lupus (patient1-17) versus 9 controls (Control1-6,Control8-10).
2011-06-23 | E-GEOD-30153 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE), also known simply as lupus, is an autoimmune disease. There is no cure for SLE. The mechanism involves an immune response by autoantibodies against a person's own tissues. However, the mechanism underlying imbalance of autoantibodies is not clear. In this experiment, peripheral blood was obtained from normal healthy donors and systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells (PBMC) were separated by Ficoll separation solution. Samples of four (total eight) donors were pooled and Samples of four (total eight) SLE patients were pooled. The aim was to characterize the mRNA profile of SLE patients compared to healthy donors and find the new target of diagnosis or treatment for SLE.
2020-08-14 | E-MTAB-7145 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus patients exhibit remarkable heterogeneity in clinical manifestations and autoantibody repertoires. This complexity poses major barrier in diagnosis and effective treatment of SLE. To address this we studied the SLE patients in groups categorized on the basis of distinct sera autoantibodies. SLE patients were segregated into three group based on the presence of autoantibodies against i) dsDNA only ii) ENA (extractable nuclear antigens) only or iii) both.
2016-11-17 | GSE80183 | GEO
Project description:Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease of unknown cause. We show here that a novel T follicular helper cell type expressing the guanine nucleotide exchange factor DOCK8 on the cell surface causes SLE. These cells, which we have designated autoantibody-inducing CD4 T (aiCD4 T) cells, are generated after resuscitation from anergy following strong TCR stimulation by antigen. When mice normally not prone to autoimmune disease were repeatedly immunized with an antigen such as OVA, they generated DOCK8+ CD4 T cells. These DOCK8+ CD4 T cells, in vivo and also upon transfer to naïve mice, induced a variety of autoantibodies and lesions characteristic of SLE. TCR repertoire analyses showed that a substantial number of novel TCR repertoires were generated in the DOCK8+ CD4 T cells, which induced novel autoantibodies upon transfer to naïve mice. DOCK8+ CD4 T cells are localized in splenic red pulp, the space immunoreactive against a variety of antigens, and specifically increased in the peripheral blood of SLE patients in association with disease activity. Anti-DOCK8 antibody treatment ameliorated the lesions induced by DOCK8+ CD4 T cells and in lupus model (NZB x W) F1 mice. Thus, when CD4 T cells are overstimulated by an external disturbance, i.e., repeatedly stimulated with antigen, to levels that surpass the system’s self-organized criticality, these cells express DOCK8 on the cell surface and acquire autoreactivity via TCR re-revision at the periphery. These DOCK8+ CD4 T cells subsequently induce a variety of autoantibodies and SLE.
2020-10-09 | GSE159240 | GEO
Project description:We previously reported the establishment of a rabbit (Oryctolagus cuniculus) model of Systemic Lupus Erythematosus (SLE) in which peptide immunization led to lupus-like autoantibody production including anti-Sm, -RNP, -SS-A, -SS-B and -dsDNA. Some neurological symptoms in form of seizures and nystagmus were observed. The animals used in the previous and in the present study were from a National Institute of Allergy and Infectious Diseases colony of rabbits that were pedigreed, immunoglobulin allotype-defined but not inbred. Their genetic heterogeneity may correspond to that found among patients of a given ethnicity. We extended the information about this rabbit model of SLE by microarray based expression profiling. We first demonstrated that human expression arrays could be used with rabbit RNA to yield information on molecular pathways. We then designed a study evaluating gene expression profiles in 8 groups of control and SLE rabbits (46 rabbits in total). Genes significantly upregulated in SLE rabbits were associated with NK cytotoxicity, antigen presentation, leukocyte migration, cytokine activity, protein kinases, RNA spliceosomal ribonucleoproteins, intracellular signaling cascades, and glutamate receptor activity. These results link increased immune activation with up-regulation of components associated with neurological and anti-RNP responses, demonstrating the utility of the rabbit SLE model to uncover biological pathways related to SLE-induced clinical symptoms, including Neuropsychiatric Lupus. Our finding of distinct gene expression patterns in rabbits that made anti-dsDNA compared to those that only made other anti-nuclear antibodies should be further investigated in subsets of SLE patients with different autoantibody profiles. An important goal of biomedical research is to translate basic findings into clinical applications. Models in inbred mice that spontaneously develop SLE, along with various mutant, transgenic and knockout models have documented a variety of genetic defects leading to SLE, but from the clinical perspective, the degree to which these findings using the inbred or homogeneous artificially mutated strains apply to individuals in heterogeneous outbred human populations is open to question. Given that there is still no cure available for SLE, it is important that we continue to explore possibilities using new animal models of SLE including neuropsychiatric lupus (NPSLE). The gene expression study reported here was conducted to expand our understanding of SLE and in particular NPSLE using our rabbit model. We reported earlier that immunization of rabbits with the SM- or GR-MAP peptides led to development of anti-nuclear autoantibodies, including anti-dsDNA, as well as neurological symptoms in the form of seizures and nystagmus in some rabbits. After establishing that it was possible to use the Affymetrix U95 human microarray for the rabbit gene expression studies, through comparative hybridization of identically prepared cRNA from human and rabbit PWBC, the human microarray was used due to lack of rabbit-specific microarrays. We describe unique gene expression changes associated with lupus like serological patterns in immunized rabbits. Our results also demonstrate that caution must be applied when choosing the structure of the carrier Multiple Antigen Peptide (MAP-peptide) for immunization. We discovered that using MAP-4 rather than MAP-8 significantly altered patterns of immune response and gene expression. Currently, microarrays specific for study of gene expression profiles are not available for rabbits. Therefore, we first conducted studies that compared identically prepared rabbit and human cRNA binding to the Affymetrix U95 microarray available for human gene expression analyses. It was determined that the human microarray could be used with rabbit cRNA to yield information on genetic pathways activated and/or suppressed in autoantibody-producing immunized rabbits. In the current report, gene expression profiles of a total of 46 rabbits, from 4 generations within a pedigreed group of control and immunized rabbits, were obtained and analyzed.
2010-07-23 | E-GEOD-23076 | biostudies-arrayexpress
Project description:Introduction: Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. Methods: We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n=45) to healthy controls (n=17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n=23) and without significant renal involvement (n=18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n=23) and longitudinal samples (88 patient visits) to test its accuracy. Results: Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B-cell activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV & X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative nephritis with 91% accuracy. Conclusions: Autoantigen microarrays are an ideal platform for identifying autoantibodies associated with both pSLE and specific clinical manifestations of pSLE. Using multiple regression analysis to integrate autoantibody and clinical data permits accurate prediction of clinical manifestations with complex etiologies in pSLE.
2015-06-10 | GSE69662 | GEO
Project description:To screen specific DNA methylation markers in systemic lupus erythematosus (SLE) patient's blood DNA, whole-blood DNAs from 6 female SLE patients and 6 female controls were analyzed by methylation microarray.
2016-12-27 | GSE57869 | GEO
Project description:Systemic lupus erythematosus (SLE) is a T and B cell-dependent autoimmune disease characterized by the appearance of autoantibodies, a global regulatory T cells (Tregs) depletion and an increase in Th17 cells. Recent studies have shown the multifaceted immunomodulatory effects of vitamin D, notably the expansion of Tregs and the decrease of Th1 and Th17 cells. A significant correlation between higher disease activity and lower serum 25-hydroxyvitamin D levels was also shown. This preliminary study suggests the beneficial role of vitamin D in SLE patients and needs to be confirmed in randomized controlled trials. In this prospective study, we evaluated the safety and the immunological effects of vitamin D supplementation in 20 SLE patients with hypovitaminosis D using transcriptomic study at M0 and M2.
2012-03-29 | E-GEOD-36941 | biostudies-arrayexpress
Project description:Recent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of DCs participating in SLE remains unclear. We profiled the lncRNAs of LPS-stimulated moDCs in SLE patients compared with healthy controls.
2018-07-19 | GSE89240 | GEO
Project description:Gene expression profiling of peripheral blood cells from patients with systemic lupus erythematosus (SLE) vs healthy individual (HI). Peripheral blood was obtained from patients with SLE (n=21) and HI (n=45). Blood samples from 45 HI are used as control.
2010-10-01 | E-GEOD-20864 | biostudies-arrayexpress