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Predicting acute GVHD by gene expression could improve liver stem cell transplant outcomes

Tampa, Fla. (July 21, 2008) Many cell transplants involve the use of stem cells from another human being (known as an allograft), which raises the major concern of the potential for acute graft-versus-host disease (GVHD). GVHD occurs when an immune response is elicited by the grafted cells against the recipient, resulting in tissue damage for the treated individual.

Presently, there are no definitive markers for predicting the development of acute graft-versus-host disease (GVHD) or its progression following the transplant of allogenic stem cells as therapy for liver cancer.

However, in a study published in the current issue CELL TRANSPLANTATON (17:5), researchers at the University of Florida offer a preliminary "molecular signature" based on gene expression for the development of acute GVHD following allogenic hematopoietic stem cell transplants (HSCT).

Despite immunosuppressive drugs, acute GVHD can develop within 100 days post-transplant. Where tissue damage in the skin, liver and gastrointestinal tract is extensive, prognosis can be poor. Although clinicians can identify a well-defined pathophysiological mechanism for acute graft-versus-host disease (GVHD), being able to uncover molecular markers for a patient's potential to develop GVHD would be a significant breakthrough.

"Our study enrolled four acute GVHD patients and four acute GVHD-free patients and noted significant differences in the expression of 1,658 genes between the control and acute GVHD patients," explained Vijay Reddy, MD, PhD, the study's lead author.

Of the 1,658 genes observed, immune-related genes showed the greatest amount of change.

"We observed a predominately pro-inflammatory gene expression profile in acute GVHD patients, consistent with our knowledge of how GVHD develops," concluded Reddy. "Perhaps the most valuable finding was having discovered the possible role for IL-27, IL-22 and Th17 cellular inflammatory responses in the development of acute GVHD."

Future research, said Reddy and colleagues, may want to address gene expression profiling of acute GVHD immediately after noting clinical symptoms, yet before immunosuppressive drugs are administered.

"Nevertheless, this is an important study to help develop biomarkers for determining who is at risk for GVHD following current and future stem cell treatments," said Dr. Paul Sanberg, Distinguished Professor at University of South Florida Health and coeditor-in-chief of Cell Transplantation.


Contact: Vijay Reddy, MD, PhD
Cell Transplantation Center of Excellence for Aging and Brain Repair

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