Modular repertoire analyses identify dynamic type I and type II interferon transcriptional signatures in adult SLE patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49454 | GEO | 2014/04/01
SECONDARY ACCESSION(S): PRJNA213965
REPOSITORIES: GEO
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Project description:Gene expression profiling (compared to healthy controls) to identify patients with active SLE disease and patients with quiescent disease 157 “SLE” and 20 “Healthy controls of SLE were followed up for up to 3 years. Clinical assessment, current treatment, laboratory results and SLEDAI score were collected at each visit (V1, V2...). SLE patients are compared to control groups.
2014-04-01 | E-GEOD-49454 | biostudies-arrayexpress
Project description:Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNFα in RA and IFNα/γ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNFα, IFNα2a and IFNγ. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFNα2a and IFNγ showed similar profiles that only partially overlapped with those induced by TNFα. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNFα-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNFα that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention. Expression profiles of human peripheral blood monocytes activated in vivo and stimulated in vitro. Monocytes from patients with SLE and RA and from healthy donors were used for generating disease-specific gene-expression profiles, where these profiles represent in vivo activation of monocytes. In addition, monocytes from healthy donors were stimulated in vitro by cytokines: TNFα, IFNα2a and IFNγ. Cytokine-specific gene-expression profiles were generated by comparing stimulated monocytes with unstimulated ones. TNFα-, IFNα2a- and IFNγ as cytokine-specific gene-expression profiles were compared with RA and SLE, as disease-specific gene-expression profiles.
2012-06-13 | E-GEOD-38351 | biostudies-arrayexpress
Project description:Mature neutrophis were freshly isolated from blood of pediatric systemic lupus erythematosus (SLE) patients and healthy donors. Illumina microarray was used to assess transcriptional changes between SLE group and Control group. To uderstand further the gene expression difference between SLE and healthy neutrofils, neutrophils from healthy donors were cultured with autologous sera, SLE sera or Interferon and microarray data was used to compare with fresh SLE neutrophils. (Expt 1) Neutrophils from 21 SLE samples (19 patients) and 12 healthy donors were isolated, and extracted RNAs were used generate microarray data. (Expt 2) Neutrophils isolated from 2 healthy children (not used in the first experiment) were cultured with autologous sera (control), Interferon alpha (100U and 1000U), and 4 SLE sera and 6 SLE sera for 6 hours and RNAs were extract for microarray experiment.
2011-03-10 | E-GEOD-27427 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is a heterogeneous disease which leads to different levels of serum autoantibodies to RNA-binding proteins (anti-RBP) and interferon-α (IFN-α), which plays an important pathogenic role in SLE, between European-American (EA) and African-American (AA) patients. We aimed to explore how IFN-related gene expression pathways differ in patients according to their ancestry and anti-RBP profile Whole blood from 33 female SLE patients and 16 matched controls from EA and AA ancestral backgrounds was analyzed through Affymetrix Gene 1.0 ST gene expression arrays and the data were further studied through Ingenuity Pathways Analysis for canonical pathway comparison. An independent replication cohort of more than 100 SLE patient samples and 30 controls was used to test the hypotheses generated by the microarray data, using qPCR to quantify gene expression.
2013-11-15 | E-GEOD-50635 | biostudies-arrayexpress
Project description:Mature neutrophis were freshly isolated from blood of pediatric systemic lupus erythematosus (SLE) patients and healthy donors. Illumina microarray was used to assess transcriptional changes between SLE group and Control group. To uderstand further the gene expression difference between SLE and healthy neutrofils, neutrophils from healthy donors were cultured with autologous sera, SLE sera or Interferon and microarray data was used to compare with fresh SLE neutrophils.
2011-03-10 | GSE27427 | GEO
Project description:Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNFα in RA and IFNα/γ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNFα, IFNα2a and IFNγ. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFNα2a and IFNγ showed similar profiles that only partially overlapped with those induced by TNFα. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNFα-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNFα that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention.
2012-06-14 | GSE38351 | GEO
Project description:Systemic lupus erythematosus (SLE) is a heterogeneous disease which leads to different levels of serum autoantibodies to RNA-binding proteins (anti-RBP) and interferon-α (IFN-α), which plays an important pathogenic role in SLE, between European-American (EA) and African-American (AA) patients. We aimed to explore how IFN-related gene expression pathways differ in patients according to their ancestry and anti-RBP profile
2013-11-15 | GSE50635 | GEO
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Project description:Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. To reveal the heterogeneity in the pathogenesis of SLE between male and female patients. PBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. Enrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.
2022-08-12 | PXD033144 | Pride
Project description:Objectives <br> Type 1 interferons (IFN-I) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-I on mixed cell populations. We aimed to define modules of IFN-I associated genes in purified leukocyte populations and use these as a basis for a detailed comparative analysis. <br>Methods<br>CD4+ and CD8+ T-cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers (HV)and gene expression determined by microarray. Modules of IFN-I associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed.<br>Results<br>1,150 of 1,288 IFN-I associated genes were specific to myeloid subsets, compared with 11 genes unique to T-cells. IFN-I genes were more highly expressed in myeloid subsets compared to T-cells. A subset of neutrophil samples from HV and conditions not classically associated with IFN-I signatures displayed increased IFN-I gene expression, whereas upregulation of IFN-I associated genes in T-cells was restricted to SLE.<br>Conclusions<br>Given the broad upregulation of IFN-I genes in neutrophils including in some HV, investigators reporting IFN-I signatures on the basis of whole blood samples should be cautious about interpreting this as evidence of bona fide IFN-I mediated pathology. Instead, specific upregulation of IFN-I associated genes in T-cells may be a useful biomarker and a further mechanism by which elevated IFN-I contributes to autoimmunity in SLE.
2016-06-01 | E-MTAB-2713 | biostudies-arrayexpress