Genome-wide DNA methylation analysis of normal and adult primary refractory immune thrombocytopenia samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205495 | GEO | 2023/06/14
REPOSITORIES: GEO
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Project description:Immune thrombocytopenia (ITP) is an autoimmune disease characterized by enhanced platelet clearance and defective platelet production. Diagnosis by exclusion and “trial-error” treatment strategies are common practice, and despite the advancement conferred by Thrombopoietin receptor agonists (TPO-RA´s), many patients remain refractory. While the existence of different pathophysiological entities is acknowledged, we are still far from stratifying and understanding ITP, a necessary step in order to provide personalized treatment options. We propose that the platelet proteome may give diagnostic and prognostic insights into the disease. As a proof of principle, we aimed to dissect the potential platelet proteome dynamics in the so-called passive and active pre-clinical ITP mouse models. To do that, we obtained the platelet proteome at the thrombocytopenic stage and upon platelet count recovery (reached naturally or upon IVIg-treatment, depending on the model). While most of the proteomic alterations were common to both ITP models, there were model-specific protein dynamics. Interestingly, we observed that not all proteomic alterations were restored when the platelet count has returned to normal. We discuss the biological processes associated with the proteome dynamics observed. Our results show that profiling the platelet proteome may have great potential to improve the management of ITP in humans.
2022-08-12 | PXD028814 | Pride
Project description:We investigated the expression profiles of plasma miRNAs in immune thrombocytopenia (ITP) patients. Peripheral blood plasma was used for Agilent miRNA expression microarray analysis to define miRNA profiles and to identify miRNAs with discriminatory levels for ITP and healthy controls. Results were further validated using quantitative realtime PCR on a larger cohort, enabling relative quantification of plasma miRNAs and defining miRNAs with diagnostic value for the disease.
2017-12-31 | GSE80401 | GEO
Project description:Immune thrombocytopenia (ITP) is an acquired autoimmune disease triggered by abnormal T cell immunity, especially the impairment of regulatory T (Treg) cells and helper T (Th) cell subsets. Decitabine, a hypomethylating agent promoting cell differentiation at low dose, has been demonstrated the function of increasing the number of mature polyploidy megakaryocytes in ITP as well as Treg cells in allogeneic transplantation. Recently, our clinical study proved that decitabine was effective and safe in the management of adult ITP patients, and nearly half showed sustained responses. However, whether low-dose decitabine has the potential in restoring immune tolerance in ITP is unknown. In our in vitro studies, we identified that low-dose decitabine could promote the generation and differentiation and enhance the immunosuppressive function of Treg cells. Furthermore, low-dose decitabine alleviated thrombocytopenia and regained the balance of Treg/Th cell subsets in active murine models of ITP. For patients who received low-dose decitabine therapy and showed responses, the quantity and function of Treg cells were substantially improved, whereas Th1 and Th17 cells were depressed compared with the pretreatment levels. Finally, immunophenotyping and next-generation RNA sequencing analysis showed that low-dose decitabine restored T cell homeostasis and decreased the level of proinflammatory cytokines along with the downregulation of STAT3 and Akt in refractory ITP patients. Therefore, our data reveal the immunomodulatory effect of decitabine and provide unique insights into the sustained response achieved by decitabine in the management of ITP patients.
2020-07-21 | GSE154703 | GEO
Project description:Purpose and Methods: Immune thrombocytopenia (ITP), an autoimmune disorder, is mainly caused by megakaryocyte dysfunction, although the underlying mechanisms remain unclear. Here, we performed single-cell transcriptome profiling of bone marrow (BM) CD34+ hematopoietic stem and progenitor cells (HSPCs) to determine defects in megakaryopoiesis in ITP. Results: Gene expression, cell-cell interactions, and transcriptional regulatory networks varied in HSPCs of ITP, particularly in natural killer/T cell progenitors and a pre-B cell subset, highlighting the selective immune aberratixon associated with defective megakaryopoiesis in ITP. CD9 can be used to enrich megakaryocyte-biased HSPCs, and CD9+Lin−CD34+CD45RA− HSPCs have the potential to be novel diagnostic and therapeutic targets in ITP. Further analysis revealed that megakaryocytic progenitors (MkP) can be divided into seven subclusters with different gene expression patterns and functions. The ITP-associated DEGs were MkP subtype-specific, with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation. Conclusions: This study comprehensively dissects defective hematopoiesis and provides novel therapeutic targets for ITP.
2022-09-03 | GSE196676 | GEO
Project description:Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children the disease resolves but in some it becomes chronic. To investigate whether the two forms of the disease are similar or separate entities we performed DNA microarray analysis of T-cells from newly diagnosed children and children with chronic ITP. We found complete separation of the expression files between the two forms of the disease. Furthermore, the gene expression of several cytokines differed between the two forms of the disease. This was also reflected in plasma with increased levels of IL-16 and TWEAK and lower levels of IL-4 in newly diagnosed compared with chronic ITP. Thus, our data indicate that the two forms of the disease may be separate entities. Microarray expression analysis of mRNA in peripheral blood T-cell of Newly diagnosed ITP vs Chronic ITP
2013-08-05 | E-GEOD-46922 | biostudies-arrayexpress
Project description:MicroRNA are small non-coding RNA molecules that regulate gene expression. To investigate the role of microRNA in ITP, we performed genome-wide expression analyses of mRNA and microRNA in T-cells from ITP patients and controls. We identified 1,915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, e.g. T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of IL-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP. Microarray expression analysis of mRNA and miRNA in peripheral blood T-cell of control and ITP patients.
2013-01-22 | E-GEOD-43178 | biostudies-arrayexpress
Project description:MicroRNA are small non-coding RNA molecules that regulate gene expression. To investigate the role of microRNA in ITP, we performed genome-wide expression analyses of mRNA and microRNA in T-cells from ITP patients and controls. We identified 1,915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, e.g. T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of IL-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP. Microarray expression analysis of mRNA and miRNA in peripheral blood T-cell of control and ITP patients.
2013-01-22 | E-GEOD-43177 | biostudies-arrayexpress
Project description:MicroRNA are small non-coding RNA molecules that regulate gene expression. To investigate the role of microRNA in ITP, we performed genome-wide expression analyses of mRNA and microRNA in T-cells from ITP patients and controls. We identified 1,915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, e.g. T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of IL-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP.
2013-01-22 | GSE43178 | GEO
Project description:MicroRNA are small non-coding RNA molecules that regulate gene expression. To investigate the role of microRNA in ITP, we performed genome-wide expression analyses of mRNA and microRNA in T-cells from ITP patients and controls. We identified 1,915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, e.g. T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of IL-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP.
2013-01-22 | GSE43177 | GEO
Project description:The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.
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