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Patients who received abatacept for graft versus host disease prophylaxis have lower peri-engraftment NETosis and less endothelial injury

ABSTRACT: Abatacept decreases risk of aGVHD in adult and pediatric patient populations, but its effect on other clinical outcomes of HSCT has not been well studied. Abatacept’s effect in reducing GVHD has been linked to T-cell dependent mechanisms, but it’s effect on neutrophils and completement activation is largely unknown. In this study we analyzed the effect of abatacept prophylaxis in clinical outcomes of HSCT and explored other potential mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE283630 | GEO | 2026/06/30

REPOSITORIES: GEO

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Patients who received abatacept for graft versus host disease prophylaxis have lower peri-engraftment NETosis and less endothelial injury

Project description:Patients who received abatacept for graft versus host disease prophylaxis have lower peri-engraftment NETosis and less endothelial injury

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Multiomic Single Cell Evaluation Reveals Inflammatory Cytokines Affect Innate Lymphoid Cell Fate After Allogeneic Stem Cell Transplantation [ChIP-Seq]

Project description:Type II innate lymphoid cells (ILC2s) maintain homeostasis and barrier integrity in mucosal tissues. Previous work has shown that in mice and humans, ILC2s fail to reconstitute after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Determining the mechanisms involved in their impaired reconstitution could improve transplant outcomes. By integrating chromatin and transcriptomic analysis of marked, transplanted ILC2s at the single cell level, we identify a previously unreported population of converted ILC1-like cells in the small intestine post-transplant. Exposure of ILC2s to proinflammatory cytokines in vitro results in a mixed ILC1-ILC2 phenotype but was able to convert only an extremely small population of ILC2s to ILC1s as observed in vivo. Whereas ILC2s protected against acute graft-versus-host disease (aGVHD) mediated-morbidity and mortality, infusion of proinflammatory cytokine-exposed ILC2s accelerated aGvHD. Finally, circulating peripheral blood mononuclear cells from patients with aGvHD have an altered ILC2-associated chromatin landscape compared to transplanted controls. These data demonstrate, for the first time, that ILC2s fail to repopulate their protective niche after allo-HSCT in part due to conversion to a pro-pathogenic population marked by an ILC1-like chromatin state, providing novel insights into the contribution of ILC plasticity to aGvHD pathogenesis after allo-HSCT.

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A clinical trial of Vedolizumab vs. placebo (dummy drug) for the prevention of intestinal Acute Graft Versus Host Disease (aGvHD), in patients undergoing allo-HSCT for a hematologic malignancy, (cancers that affect the blood and/or lymphatic system).

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Gene expression profiles of peripheral blood mononuclear cells before abatacept treatment in rheumatoid arthritis patients.

Project description:To explore markers which predict the efficacy of abatacept in rheumatoid arthritis, peripheral blood mononuclear cells were obtained before abatacept treatment.

2023-04-10 | GSE224842 | GEO

Rheumatoid arthritis synovium response to abatacept

Project description:Our goal was to assess for the histological and transcriptomic effects of Abatacept on RA synovia, and to compare them with previously published data from four other DMARDs: Tocilizumab, Rituximab, Methotrexate and Adalimumab.

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Gene expression profiling in Abatacept treated Rheumatoid Arthritis patients according to response

Project description:The objective of this study was to identify specific gene expression profiles able to predict the response of rheumatoid arthritis patients treated with methotrexate /abatacept (Aba). Thirty six RA patients were received Abatacept. The drug efficacy was evaluated with the DAS28 score after 6 months of treatment according to the EULAR response criteria. Among 36 Aba RA patients, 17 were responders and 19 were classified as no-responders. A blood sample was carried out in patients just before the first injection of treatment in PaxGene tubes. Two color experiments : patient(Cy5)/Control pool (Cy3).

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RNA_seq analysis on Tfh and Treg before and after abatacept treatment

Project description:Analysis of transcriptome data identified 96, 64 and 3 genes that were differentially expressed (DE, adj. P value < 0.05) following abatacept treatment in Tfh, Treg and CD4+CD45RO+PD1+CXCR5- T cells, respectively. We determined if abatacept treatment altered the core transcriptional profiles of Tfh and Treg lineages by comparing gene expression of bulk sorted Treg and Tfh cells from cryopreserved PBMCs at baseline, week 24, and after abatacept withdrawal. Analysis of differentially expressed (DE) genes in Tfh was performed using Gene Ontology (GO) term enrichment analysis. This analysis revealed 9 significantly enriched GO categories, which were related to processes involved in cell division and proliferation. DE genes in the enriched GO categories showed a highly significant correlation in Tfh and Treg cells, further highlighting the similarity in the response of these two populations to abatacept. In contrast to Tfh and Treg, acatacept had a minimal impact on CD4+CD45RO+PD1+CXCR5- T cells.

2018-12-27 | GSE121827 | GEO

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Project description:Lymphoid committed CD34+lin-CD10+CD24- progenitors undergo a rebound at month 3 after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the absence of acute graft-versus-host disease (aGVHD). Here, we analyzed transcriptional programs of cell-sorted circulating lymphoid committed progenitors and CD34+Lin-CD10- non lymphoid progenitors in 11 allo-HSCT patients having (n=5) or not developed (n=6) grade 2 or 3 aGVHD and in 7 age-matched healthy donors. Major deregulated pathways included protein synthesis, energy production, cell cycle regulation and cytoskeleton organization. Notably, genes from protein biogenesis, translation machinery and cell cycle (CDK6) were over-expressed in progenitors from patients in the absence of aGVHD compared with healthy donors and patients affected by aGVHD. Expression of many genes from the mitochondrial oxidative phosphorylation metabolic pathway leading to ATP production were more specifically increased in lymphoid committed progenitors in absence of aGVHD. This was also the case for genes involved in cell mobilization such as those regulating Rho GTPases activity. In all, we show that circulating lymphoid committed progenitors undergo profound changes in metabolism favoring cell proliferation, energy production and cell mobilization after allo-HSCT in humans. These mechanisms are abolished in case of aGVHD or its treatment, indicating a persistent cell-intrinsic defect after exit from bone marrow.

2018-11-14 | GSE75344 | GEO

Single-cell transcriptome analysis reveals atypical monocytes circulating ahead of acute graft-versus-host disease clinical onset

Project description:Acute graft-versus-host disease (aGVHD) represents the rejection of the skin, gut and liver tissues of the recipient of an allogenic hematopoietic stem cell transplantation (HSCT) by the donor T-cells. The onset of aGVHD is often rapid and its evolution unpredictable. We undertook the single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected before aGVHD clinical onset in three patients and at aGVHD diagnosis in one, using four HSCT recipients who remained free of aGVHD as controls. This analysis unveiled the presence in the circulation of particular subpopulations of monocytes and cytotoxic T cells (CTLs) in pre-aGVHD samples up to 18 days before clinical disease. These pre-aGVHD monocytes were characterized by an upregulation of the M2 polarity marker CD163, and the transmembrane protein SIGLEC1/CD169, while their CTL counterparts stood out for the upregulation of the CXCL10 receptor CXCR3 and the antigenic stimulation marker CD70. The occurrence of CD163/CD169-co-expressing monocytes upstream of aGVHD onset was validated using RNAseq data from an independent cohort and by flow cytometry of blood samples. These findings point to potential early diagnostic tools and preventive therapeutic strategies for aGVHD.

2025-07-07 | GSE269338 | GEO

Complement lysis affects engraftment and efficacy of human mesenchymal stromal cell-based therapy

Project description:Acute Graft-versus-Host-Disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplantation of immunosuppressive human mesenchymal stromal cells (hMSCs) can protect against aGVHD post HSCT; however, their efficacy is limited by poor engraftment and survival. Moreover, infused MSCs can be damaged by activated complement, yet strategies to minimise complement injury of hMSCs and improve their survival are limited. Here, we report that hMSCs derived from three tissues divergently protected against aGVHD in a mouse model of this disease. Adipose tissue (AT)-hMSCs preferentially suppressed complement in vitro and in vivo, resisted complement lysis and survived better after transplantation when compared to bone marrow (BM)- and umbilical cord (UC)-hMSCs. AT-hMSCs also prolonged survival and improved the symptoms and pathological features of aGVHD.

2022-12-07 | GSE219227 | GEO

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