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Prediction of graft-versus-host disease in humans by donor gene expression profiling

ABSTRACT: Graft-versus-host disease (GVHD) results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantion (AHCT). Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be “stronger alloresponders” than others, and consequently more likely to elicit GVHD. To this end, we analyzed the gene expression profile of CD4 and CD8 T cells from 50 AHCT donors. We found that pre-AHCT gene expression profiling segregates donors whose recipient suffered from GVHD or not. The “dangerous donor” trait (GVHD+ recipient) is under polygenic control and is shaped by the activity of genes that regulate diverse cell functions including TGF-β signaling and cell proliferation. We also performed gene expression profiling in T cells harvested from 40 AHCT recipients on day 365 post-AHCT. The donor gene profile defined on day 0 showed exceedingly strong correlation with that of recipient CD4 and CD8 T cells harvested one year post-AHCT. These data suggest that donor gene profiles linked with GVHD were largely imprinted at the hematopoietic stem cell level. The ability to discriminate strong and weak alloresponders using gene expression profiling could pave the way to personalized transplantation medicine. Keywords: comparative gene profile, cell type comparaison, GVHD+, GVHD-

ORGANISM(S): Homo sapiens

PROVIDER: GSE4624 | GEO | 2007/03/27

SECONDARY ACCESSION(S): PRJNA95337

REPOSITORIES: GEO

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