Altered thymic NKT1 and NKT2 differentiation in murine haploidentical bone marrow transplantation with chronic GvHD
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PROVIDER: PRJNA950927 | ENA |
REPOSITORIES: ENA
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Project description:To investigate whether intermediate iNKT precursor cells were affected in GvHD mice along the differentiation journey toward mature effector cells, we performed scRNA-seq on thymic iNKT precursors from BMT mice with and without cGvHD and non-BMT mice. We identified Multiple early and late NKT1 precursor clusters and further explored the development of NKT1 under physiological as well as transplantation condition.
2023-07-31 | GSE228645 | GEO
Project description:Lymphocyte subsets (CD8, CD4 Tconv, NK cells) were sorted from patients' peripheral blood obtained on day 28 after haploidentical-donor allogeneic bone marrow transplantation followed by posttransplant cyclophosphamide (PTCy), tacrolimus, and MMF as GVHD prophylaxis (NCT00796562). Cohort of patients developed GVHD, or remained GVHD-free. Cohort of patients developed disease relapse, or remained relapse-free. RNA-sequencing was performed to analyze the transcriptional landscape of alloresponse in post-PTCy breakthrough GVHD and relapse.
2021-09-28 | GSE182612 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE10512: Gene Expression Profiles of PBMC Subsets in Acute GVHD Following Cord Blood Transplantation (IMS v.1) GSE10513: Gene Expression Profiles of PBMC Subsets in Acute GVHD Following Cord Blood Transplantation (IMS v.2) Keywords: SuperSeries Refer to individual Series
2008-12-21 | E-GEOD-10572 | biostudies-arrayexpress
Project description:Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although post-transplant cyclophosphamide (PtCy) has improved graft vs. host disease (GvHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. IFN-γ and IL-6 are central in the pathophysiology of GvHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase (JAK)-1. We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy-haplo-HCT to mitigate these complications and improve overall survival. This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GvHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day -3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2-5 CRS. There were no cases of primary graft failure. No patients developed grade 3-4 aGvHD through day +180. The cumulative incidence of grade 2 aGvHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GvHD was 5%. The cumulative incidence of relapse at 2 years was 14%. Overall survival (OS) at 1 year was 80%. The cumulative incidence of nonrelapse mortality at day 180 was 8%. Itacitinib, when added to standard GvHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GvHD, NRM and encouraging rates of GvHD-free relapse-free survival (GRFS) and OS after haplo-HCT.
2024-11-15 | GSE282021 | GEO
Project description:In comparison with allogeneic hematopoietic stem cell transplantation using other sources, umbilical cord blood transplantation (UCBT) offers substantial clinical advantages including a lower incidence and severity of acute graft-versus-host disease (GVHD) despite the use of allogeneic UCB stem cells with more disparate HLA. However, detailed pathophysiology of acute GVHD developed after UCBT has not yet been clarified. Here, we examined the roles of inflammatory cells in the pathogenesis of acute GVHD following UCBT, by expression profiling of a total of 615 genes in each of 4 subsets (CD4+, CD8+, CD14+, and CD56+) of peripheral blood mononuclear cells (PBMCs), which were taken from 5 patients with hematologic malignancy, in whom acute GVHD had developed after UCBT. By comparing expression profiles measured during acute GVHD with those measured upon discharge (recovery phase), for each subset of PBMCs, we identified immuno-regulatory genes which were assumed to be linked to the pathogenesis of acute GVHD. Keywords: disease state analysis CD4+, CD8+, CD14+, and CD56+ cell subsets were isolated from the peripheral blood mononuclear cells (PBMCs) of 5 patients with hematologic malignancy, in whom acute GVHD had developed after cord blood transplantation. PBMCs were taken twice â during acute GVHD phase and upon discharge (recovery phase), from each patient. By using a custom-made fibrous oligonucleotide DNA microarray Genopal (Mitsubishi Rayon), we compared expression profiles of 615 unique genes measured during acute GVHD with those measured upon discharge (recovery phase), for each subset of PBMCs.
2010-05-15 | E-GEOD-10513 | biostudies-arrayexpress
Project description:In comparison with allogeneic hematopoietic stem cell transplantation using other sources, umbilical cord blood transplantation (UCBT) offers substantial clinical advantages including a lower incidence and severity of acute graft-versus-host disease (GVHD) despite the use of allogeneic UCB stem cells with more disparate HLA. However, detailed pathophysiology of acute GVHD developed after UCBT has not yet been clarified. Here, we examined the roles of inflammatory cells in the pathogenesis of acute GVHD following UCBT, by expression profiling of a total of 595 genes in each of 4 subsets (CD4+, CD8+, CD14+, and CD56+) of peripheral blood mononuclear cells (PBMCs), which were taken from 3 patients with hematologic malignancy, in whom acute GVHD had developed after UCBT. We compared expression profiles measured during acute GVHD with those measured opon discharge (recovery phase), for each subset of PBMCs to identify immuno-regulatory genes which were assumed to be linked to the pathogenesis of acute GVHD. Keywords: disease state analysis Peripheral blood mononuclear cells (PBMCs) were taken from 3 patients with hematologic malignancy, in whom acute GVHD had developed after cord blood transplantation. CD4+, CD8+, CD14+, and CD56+ cell subsets were isolated from the PBMCs of 2 patients, while only CD8+ and CD56+ cell subsets were isolated from the PBMCs of a patient. PBMCs were taken twice - during acute GVHD phase and upon discharge (recovery phase), from each patient. By using a custom-made fibrous oligonucleotide DNA microarray Genopal (Mitsubishi Rayon), we compared expression profiles of 595 unique genes measured during acute GVHD with those measured upon discharge (recovery phase), for each subset of PBMCs.
2010-05-15 | E-GEOD-10512 | biostudies-arrayexpress
Project description:BACKGROUND - IL-6 mediates graft-versus-host disease (GVHD) in experimental allogeneic stem cell transplantation (alloSCT) and is an attractive therapeutic target. METHODS - A registered phase I/II study (ACTRN12612000726853) of IL-6 receptor (IL-6R) neutralizing antibody administration on day -1 to patients receiving full or reduced-intensity conditioning (RIC) and alloSCT from HLA-matched sibling or unrelated donors with standard cyclosporin and methotrexate GVHD prophylaxis. The primary endpoint was incidence of grade II-IV acute GVHD. Outcomes were compared to a non-randomized but contemporaneous group of study patients receiving the same alloSCT in the absence of IL-6R mAb. FINDINGS - Cytokine and pharmacokinetic analysis confirmed transient IL-6 dysregulation in the first month after alloSCT with complete inhibition following IL-6R mAb administration. With median follow up of 497 days, the incidence of grade II-IV GVHD was 12.5% in recipients of IL-6R inhibition (n = 48) versus 41.5% in the (n = 53) control cohort (P = 0.001). Low rates of acute GVHD were noted in patients receiving IL-6R inhibition relative to control patients following both myeloablative (12.5% vs. 46.4%, P = 0.03) and RIC (12.5% vs. 36.0%, P = 0.04). The incidence of severe (grade III/IV) acute GVHD was 4.2% in recipients of IL-6R inhibition versus 20.8% in the control cohort (P = 0.012). Relapse and chronic GVHD were unchanged. Immune reconstitution was preserved in recipients of IL-6R inhibition, but qualitatively modified with suppression of known pathogenic STAT3-dependent pathways. INTERPRETATION - IL-6 is the principal detectable and dysregulated cytokine secreted after alloSCT and its inhibition is a potential new and simple strategy to protect from acute GVHD despite robust immune reconstitution and a sustained graft-versus-leukemia effect. Single colour, Illumina Human HT12v4 Beadarrays.
2014-09-09 | E-GEOD-61201 | biostudies-arrayexpress
Project description:Regulatory T cells restore tolerance in preclinical models of immune-mediated diseases and are therefore a promising alternative to conventional immune-suppression for preventing graft-versus-host disease (GvHD) in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Adaptive CD4+ Type 1 regulatory T (Tr1) cells specific for alloantigens are induced in vitro by interleukin-10 (IL-10). Therefore, we evaluated whether infusion of Tr1 cells could promote immune-competence to foreign antigens and long-term alloantigen-specific tolerance. In this phase 1-2 trial, we performed adoptive transfer with IL-10-induced alloantigen-specific Tr1 cells (IL-10-DLI), without immune-suppression, in patients with high-risk hematopoietic malignancies transplanted with CD34+ cells from haploidentical donors. Donor T cells, primed ex vivo with host antigen-presenting-cells and IL-10, are anergic towards host-HLA antigens and contain host-specific Tr1 cells but also memory T cells able to respond to pathogens. Nineteen patients were enrolled in the trial. Twelve received IL-10-DLI. Seven were not evaluable because of early death/relapse, whereas five immune-reconstituted (>100/µl CD3+ T cells) at median day 28 after IL-10-DLI. T-cell counts and function progressively normalized in patients who received 105 CD3+ T cells/kg, whereas a higher dose (3x105 CD3+ T cells/kg) caused acute grade III GvHD in one patient. Four patients are alive, in disease remission and immune-suppression-free at a median follow-up of 3.3 years, three of them were analyzed by microarrays; their T-cell receptor repertoire and gene expression profiles are comparable to those of healthy subjects. Cell therapy with IL-10-DLI is feasible, safe, and provides immune-competence. This trial is the first step towards widespread use of Tr1 cells as adjuvant treatment in allogeneic HSCT (IS/11/6172/8309/8391). Keywords: classification of clinical samples Whole blood samples of three healthy donors and three different patients collected at various time points after hematopoietic stem cell transplantation (HSCT) before and after the subsequent administration of IL-10 anergized T cells were analysed on a custom Agilent 8x15K 60mer oligonucleotide microarray encomprising 4610 probes in triplicates. The microarray is dedicated to transplantation research and was designed based on current literature and published and unpublished data provided by the RISET consortium. For the probe selection procedure we specially focused on the detection of multiple transcript variants of a gene, on optimized hybridization properties of the probes, and on the avoidance of crosshybridization. The RISET 1.0 platform (GPL10370) is a precursor of the RISET 2.0 microarray (GPL8136).
2015-12-14 | E-GEOD-21885 | biostudies-arrayexpress
Project description:In comparison with allogeneic hematopoietic stem cell transplantation using other sources, umbilical cord blood transplantation (UCBT) offers substantial clinical advantages including a lower incidence and severity of acute graft-versus-host disease (GVHD) despite the use of allogeneic UCB stem cells with more disparate HLA. However, detailed pathophysiology of acute GVHD developed after UCBT has not yet been clarified. Here, we examined the roles of inflammatory cells in the pathogenesis of acute GVHD following UCBT, by expression profiling of a total of 615 genes in each of 4 subsets (CD4+, CD8+, CD14+, and CD56+) of peripheral blood mononuclear cells (PBMCs), which were taken from 5 patients with hematologic malignancy, in whom acute GVHD had developed after UCBT. By comparing expression profiles measured during acute GVHD with those measured upon discharge (recovery phase), for each subset of PBMCs, we identified immuno-regulatory genes which were assumed to be linked to the pathogenesis of acute GVHD. Keywords: disease state analysis
2008-12-22 | GSE10513 | GEO
Project description:In comparison with allogeneic hematopoietic stem cell transplantation using other sources, umbilical cord blood transplantation (UCBT) offers substantial clinical advantages including a lower incidence and severity of acute graft-versus-host disease (GVHD) despite the use of allogeneic UCB stem cells with more disparate HLA. However, detailed pathophysiology of acute GVHD developed after UCBT has not yet been clarified. Here, we examined the roles of inflammatory cells in the pathogenesis of acute GVHD following UCBT, by expression profiling of a total of 595 genes in each of 4 subsets (CD4+, CD8+, CD14+, and CD56+) of peripheral blood mononuclear cells (PBMCs), which were taken from 3 patients with hematologic malignancy, in whom acute GVHD had developed after UCBT. We compared expression profiles measured during acute GVHD with those measured opon discharge (recovery phase), for each subset of PBMCs to identify immuno-regulatory genes which were assumed to be linked to the pathogenesis of acute GVHD. Keywords: disease state analysis
2008-12-22 | GSE10512 | GEO