2007/01/26 by Chantal Baron, Roland Somogyi, Larry D. Greller +10 · 102 citations
Medicine · Immunology and Microbiology · #Hematopoietic Stem Cell Transplantation #T-cell and B-cell Immunology #Acute Myeloid Leukemia Research #Gene expression profiling #Graft-versus-host disease #Gene expression #Transplantation #Immunology #CD8 #Biology #Gene #Hematopoietic stem cell transplantation #Hematopoietic cell #Disease #Haematopoiesis #Medicine #Immune system #Stem cell #Genetics #Pathology #Internal medicine
paper · doi:10.1371/journal.pmed.0040023
published in PLoS Medicine 4(1), e23 (Public Library of Science)
openalex publication_date 2007/01/26 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/08
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.