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Transcriptome analysis of acute graft-versus-host disease in children

ABSTRACT: Transcriptome analysis of acute graft-versus-host disease in children

PROVIDER: PRJNA706045 | ENA |

REPOSITORIES: ENA

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Transcriptome analysis of acute graft-versus-host disease in children

Project description:Steroid-refractory gastrointestinal graft-versus-host disease (GI GVHD) is a major barrier to successful hematopoietic stem cell transplant (HSCT). Poor understanding of the pathophysiology of GI GVHD contributes to continued poor outcomes and high mortality rates. We therefore obtained rectosigmoidal mucosal biopsies from post-HSCT patients with GI GVHD and submitted them to RNA-sequencing in order to transcriptomally characterize GI GVHD. These were compared to patients undergoing endoscopy for routine clinical indications. Using single end, 50bp reads processed using Kallisto using genome annotations from Gencode v24 with transcripts per million as the output. We included 14,239 trancsripts in our analysis, where we compared GVHD vs non-GVHD with significance defined as FDR<0.05 and FC 1.5 using R package DESeq2. We identified 164 key genes, of which 141 were upregulated in GVHD, and were ontologically related to microbial response, key immune effectors, and cell migration/chemotaxis. Down-regulated genes were related to nutrient metabolism. Additionally, we performed WGCNA that highlighted ERK as a key upregulated pathway in GI GVHD.

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Beclomethasone in Treating Patients With Graft-Versus-Host Disease of the Esophagus, Stomach, Small Intestine, or Colon

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Tauroursodeoxycholic acid prevents acute graft-versus-host disease in mice by regulating intestinal apoptosis and inflammation

Project description:The effect of tauroursodeoxycholic acid on the development of acute graft-versus-host disease was tested in a murine allogeneic stem cell transplantation model. TUDCA was shown to reduce acute GVHD by reducing intestinal antigen presentation and following apoptosis and increasing the viability of intestinal epithelial cells.

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CD8+ T cell response in the Act-mOVA/OT-I model of acute graft versus host disease

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Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

Project description:This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient’s immune system from rejecting the donor’s stem cells. Healthy stem cells from a donor that are infused into the patient help the patient’s bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body’s normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.

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