Donor Gene Expression Profiling May Help Predict GVHD

By Megan Rauscher

NEW YORK FEB 06, 2007 (Reuters Health) - In allogeneic hematopoietic cell transplantation (AHCT), differential gene expression in donor CD4+ and CD8+ T cells is predictive of the risk of graft-versus-host disease (GVHD) in the recipient, researchers from Quebec, Canada report in the January issue of PLoS Medicine.

"Our findings strongly suggest that the donor gene expression profile has a dominant influence on the occurrence of GVHD in the recipient," Dr. Claude Perreault from University of Montreal told Reuters Health.

"The ability to discriminate strong and weak alloresponders using gene expression profiling could pave the way to personalized transplantation medicine," he added.

GVHD due to rejection of the recipient by donor T lymphocytes present in the graft, the researcher explained, is the main barrier in AHCT. Histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD.  An unexplored hypothesis is that some donors might be stronger alloresponders than others.

Using microarray technology, the Quebec team measured the gene expression profiles of CD4+ and CD8+ T cells from 50 AHCT donors and found that pre-AHCT gene expression profiling segregated donors whose recipient developed GVHD from those who did not.

"Using quantitative PCR, established statistical tests and analysis of multiple independent training-test data sets, we found that the dangerous donor trait (GVHD+ recipient) is under polygenic control and is shaped by the activity of genes that regulate TGF-beta signaling and cell proliferation," Dr. Perreault said.

Taken together, Dr. Perreault predicts that donor gene expression profiling "could help in the selection of low-risk donors for AHCT and in the tailoring the immunosuppressive regimens given to the recipient according to the risk of GVHD."

SOURCE:

• PLos Med 2007;4:e23.