Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA239638 | ENA |
REPOSITORIES: ENA
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Project description:Background/Purpose: Systemic lupus erythematosus (SLE) is a complex multi-system autoimmune disease of uncertain etiology. Patients from different ancestral backgrounds demonstrate differences in clinical manifestations and autoantibody profiles. In this study we examined genome-wide transcriptional patterns in major immune cell subsets across different ancestral backgrounds. Methods: Peripheral blood was collected from 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA controls, and 5 EA controls. CD4+ T-cells, CD8+ T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on an Illumina HumanHT-12 V4 expression BeadChip array (n=208 arrays). Differentially expressed genes (DEGs) were determined by comparing cases and controls of the same ancestral background. Results: The overlap in DEG lists between different cell types from the same ancestral background was very modest (<1%). Typically between 5-10% of DEGs were shared when comparing the same cell type between different ancestral backgrounds (for ex. CD20 AA vs. CD20 EA). Quantitative measurement of global IFN-stimulated gene (ISG) expression revealed that AA subjects demonstrated more concordance across all studied cell types. Two subgroups of patients were identified based on the ISG expression profiles. One subgroup showed higher ISGs expression in all cell types, and the other subgroup had higherISG expression only in T and B lymphocytes but not in monocytes. The correlation of ISG expression with medication data revealed that only the B cells had lower ISG expression in patients taking immunosuppressants, while ISG expression in the other cell types did not differ based upon medication use. Conclusion: We find striking differences in gene expression between different immune cell subsets and between ancestral backgrounds in SLE patients. The IFN signature is diverse, with different transcripts represented in different cell populations, and signature-positive cell subsets differed in EA vs. AA patients. We also find that treatment with the immunosuppressive agents correlates with the down-regulation of B cell ISG expression, and this was not observed in other cell types. Peripheral blood was collected from 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA controls, and 5 EA controls. CD4+ T-cells, CD8+ T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on an Illumina HumanHT-12 V4 expression BeadChip array (n=208 arrays).
2015-05-15 | E-GEOD-55447 | biostudies-arrayexpress
Project description:Background/Purpose: Systemic lupus erythematosus (SLE) is a complex multi-system autoimmune disease of uncertain etiology. Patients from different ancestral backgrounds demonstrate differences in clinical manifestations and autoantibody profiles. In this study we examined genome-wide transcriptional patterns in major immune cell subsets across different ancestral backgrounds. Methods: Peripheral blood was collected from 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA controls, and 5 EA controls. CD4+ T-cells, CD8+ T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on an Illumina HumanHT-12 V4 expression BeadChip array (n=208 arrays). Differentially expressed genes (DEGs) were determined by comparing cases and controls of the same ancestral background. Results: The overlap in DEG lists between different cell types from the same ancestral background was very modest (<1%). Typically between 5-10% of DEGs were shared when comparing the same cell type between different ancestral backgrounds (for ex. CD20 AA vs. CD20 EA). Quantitative measurement of global IFN-stimulated gene (ISG) expression revealed that AA subjects demonstrated more concordance across all studied cell types. Two subgroups of patients were identified based on the ISG expression profiles. One subgroup showed higher ISGs expression in all cell types, and the other subgroup had higherISG expression only in T and B lymphocytes but not in monocytes. The correlation of ISG expression with medication data revealed that only the B cells had lower ISG expression in patients taking immunosuppressants, while ISG expression in the other cell types did not differ based upon medication use. Conclusion: We find striking differences in gene expression between different immune cell subsets and between ancestral backgrounds in SLE patients. The IFN signature is diverse, with different transcripts represented in different cell populations, and signature-positive cell subsets differed in EA vs. AA patients. We also find that treatment with the immunosuppressive agents correlates with the down-regulation of B cell ISG expression, and this was not observed in other cell types.
2015-05-15 | GSE55447 | 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 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:Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by systemic inflammation that involves various immune cell types. Monocytes are central players in promoting and regulating inflammation. Different monocyte subsets exist and change their proportions during physiological immune responses and under pathological conditions, including SLE, supporting different roles in inflammatory responses. In this study, we obtained the epigenetic and transcriptomic profiles of the three monocyte subsets, classical, intermediate and non-classical monocytes in an SLE cohort. We found different common and subset-specific alterations. While SLE classical monocytes had a stronger proinflammatory profile with an important interferon influence priming them towards macrophage differentiation, non-classical monocytes had a phenotype related to T cell differentiation regulation, with several indications pointing towards a Th17 promoting behavior. Integration of these bulk datasets with single-cell RNA-seq data of an SLE cohort shed light on the heterogeneity of our monocytes, confirming the interferon signature profile of classical monocytes and pointing towards intermediate and non-classical populations associated with exacerbated complement activation pathways, among others. With this analysis, we confirm the differential role of monocyte subsets in the pathogenesis of SLE and give insight into their regulatory mechanisms.
2024-10-30 | GSE249639 | GEO
Project description:Comparison of two B cell subsets isolated from healthy individuals after stimulation in vitro with SLE-related immune complexes and in the presence of plasmacytoid dendritic cells.
2017-09-07 | E-MTAB-5740 | biostudies-arrayexpress
Project description:Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by systemic inflammation that involves various immune cell types. Monocytes play a central role in promoting and regulating inflammation. Peripheral blood classical monocytes subsequently differentiate into intermediate monocytes and then non-classical monocytes, assuming diverse roles and undergoing changes in their proportions during physiological immune responses and pathological conditions, including SLE. In this study, we obtained the epigenetic and transcriptomic profiles of these three monocyte subsets in an SLE cohort. We found different common and subset-specific alterations. While SLE classical monocytes had a stronger proinflammatory profile with an important interferon influence priming them towards macrophage differentiation, non-classical monocytes had a phenotype related to T cell differentiation regulation, with several indications pointing towards a Th17 promoting behavior. Integration of these bulk datasets with single-cell RNA-seq data of an SLE cohort shed light on the heterogeneity of our monocytes, confirming the interferon signature profile of classical monocytes and pointing towards intermediate and non-classical populations associated with exacerbated complement activation pathways, among others. Our results indicate a subversion of the epigenome and transcriptome in monocyte differentiation toward non-classical subsets in SLE, involving the STAT1 pathway and impacting function in relation to disease activity.
2024-10-30 | GSE249619 | GEO
Project description:SLE is characterized by the production of autoantibodies that arise from the B cell lineage. Therefore, we sought to assess the epigenetic and transcriptome profiles of distinct B cell subsets known to be expanded in SLE from healthy and SLE subjects. These data define the differentiation heirarchy of B cell subsets and the epigenetic and transcriptional consequences of SLE on human B cells.
2019-05-17 | GSE118255 | GEO
Project description:SLE is characterized by the production of autoantibodies that arise from the B cell lineage. Therefore, we sought to assess the epigenetic and transcriptome profiles of distinct B cell subsets known to be expanded in SLE from healthy and SLE subjects. These data define the differentiation heirarchy of B cell subsets and the epigenetic and transcriptional consequences of SLE on human B cells.
2019-05-17 | GSE118254 | GEO
Project description:SLE is characterized by the production of autoantibodies that arise from the B cell lineage. Therefore, we sought to assess the epigenetic and transcriptome profiles of distinct B cell subsets known to be expanded in SLE from healthy and SLE subjects. These data define the differentiation heirarchy of B cell subsets and the epigenetic and transcriptional consequences of SLE on human B cells.
2019-05-17 | GSE118253 | GEO
Project description:For rapidly mutating viruses such as influenza viruses and SARS-CoV-2, immune memory recalled by antigenically drifted variants primarily comprises antibodies that cross-react to the priming strain rather than de novo elicited responses, a phenomenon termed original antigenic sin or immune imprinting. The composition and functionality of de novo responses elicited by variant exposures remain unclear. Here, we isolated and characterized hundreds of recall and de novo neutralizing monoclonal antibodies after sequential exposures to SARS-CoV-2 variants in ancestral-imprinted humans. De novo variant type-specific antibodies used different V(D)J genes that were closer to germline sequence, potently neutralized future variants, and targeted distinct receptor binding domain epitopes compared to ancestral cross-reactive (recall) antibodies. Nevertheless, neutralizing responses to the updated 2024-2025 booster were predominantly ancestral cross-reactive. These results reveal the distinct contributions of imprinted and de novo antibodies to a balanced immune response and underscore the benefit of updated booster vaccines which augment both subsets.
2026-07-06 | GSE325987 | GEO