Prediction of Graft-Versus-Host Disease in Humans by Donor Gene-Expression Profiling

Abstract

BACKGROUND Graft-versus-host disease (GVHD) results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantation (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. METHODS AND FINDINGS To this end, we measured the gene-expression profiles of CD4(+) and CD8(+) T cells from 50 AHCT donors with microarrays. We report that pre-AHCT gene-expression profiling segregates donors whose recipient suffered from GVHD or not. Using quantitative PCR, established statistical tests, and analysis of multiple independent training-test datasets, we found that for chronic GVHD the "dangerous donor" trait (occurrence of GVHD in the recipient) is under polygenic control and is shaped by the activity of genes that regulate transforming growth factor-beta signaling and cell proliferation. CONCLUSIONS These findings strongly suggest that the donor gene-expression profile has a dominant influence on the occurrence of GVHD in the recipient. The ability to discriminate strong and weak alloresponders using gene-expression profiling could pave the way to personalized transplantation medicine.

Extracted Key Phrases

8 Figures and Tables

0100200300'05'06'07'08'09'10'11'12'13'14'15'16'17
Citations per Year

870 Citations

Semantic Scholar estimates that this publication has 870 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Baron2007PredictionOG, title={Prediction of Graft-Versus-Host Disease in Humans by Donor Gene-Expression Profiling}, author={Chantal Baron and Roland Somogyi and Larry D. Greller and Vincent Rineau and Peter Wilkinson and Carolyn R Cho and Mark J Cameron and David J. Kelvin and Pierre Chagnon and Denis-Claude Roy and Lambert Busque and Rafick-Pierre Sekaly and Claude Perreault}, journal={PLoS Medicine}, year={2007}, volume={4}, pages={1481 - 1555} }