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FK506 and Lactobacillus acidophilus Ameliorate Acute Graft-Versus-Host Disease by Modulating the T Helper 17/Regulatory T-Cell Balance

ABSTRACT: Graft-versus-host disease (GvHD) is critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation. The intestinal microbiome is a target for the development of novel therapies for GvHD. We determined the effect of the combination of tacrolimus (FK506) and Lactobacillus acidophilus on GvHD.

ORGANISM(S): Mus musculus

PROVIDER: GSE174214 | GEO | 2021/05/11

REPOSITORIES: GEO

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Acute graft-versus-host disease (gene expression profiling)

Project description:Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for high-risk hematological malignancies, yet a major complication associated with this therapy is acute graft-versus-host disease (GVHD). Despite a well-defined pathophysiological mechanism, there are no definitive markers for predicting acute GVHD development or progression to advanced stages. In the current study, we enrolled four acute GVHD and four acute GVHD-free recipients of allogeneic HSCT and collected peripheral blood just prior to onset of clinical acute GVHD for analysis on Affymetrix GeneChip Human Genome U133 Plus 2.0 microarrays. We noted significant differences in expression of 1,658 genes between control and acute GVHD patients, based on an analysis of covariance (ANCOVA) by type of transplant, a pooled error estimate, and a false discovery rate (FDR) of 10%. In conclusion, we offer the first report of a preliminary molecular signature of acute GVHD in allogeneic HSCT patients.

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Project description:The aim of this study is to assess the Fecal Microbiota Transplantation (FMT) efficacy in the prevention of allogeneic hematopoietic stem cell transplantation (allo-HSCT) complications and particularly Graft versus Host Disease (GvHD). The hypothesis of this study is that allogeneic FMT may improve outcomes of these patients.

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Glycolytic metabolism of pathogenic T cells enables early detection of GvHD by 13C-MRI.

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