TORONTO - Canadian researchers believe they have come up with a way to predict whether transplants from specific bone marrow donors are likely to trigger rejection -- an advance that could help doctors weed out so-called "dangerous donors'' and cut back on immune suppressant drugs for some transplant recipients.
If corroborated, their findings could lower the risk of graft-versus-host disease for bone marrow recipients. They could eventually also help predict which recipients will reject transplanted kidneys, livers and other solid organs, allowing doctors to tailor post-transplant drug regimes according to the recipient's risk.
"I think it would become a routine test,'' senior author Dr. Claude Perreault said Monday of the finding's applicability for bone marrow transplants. "It would be easy and cheap.''
The study was published in the journal Public Library of Science Medicine.
Perreault is with the Institute of Research in Immunology and Cancer at the University of Montreal. His co-authors include researchers from Montreal's Maisonneuve-Rosemont Hospital, the Lady Davis Institute for Medical Research at Montreal's Jewish General Hospital and the Toronto General Research Institute.
The thinking on transplants has been that when a person gets a solid organ transplant _ a donated kidney or a portion of a liver _ the recipient's immune system must be suppressed for life to ensure that it does not turn against and destroy what it would see as a foreign organ.
With bone marrow, doctors are essentially transplanting the donor's immune system _ produced in the marrow _ into the recipient. And it is that donated immune system that turns against the recipient. If that process is not checked by immune suppressing drugs, potentially fatal graft-versus-host disease develops.
However, early attempts to transplant bone marrow showed that about 25 per cent of recipients didn't develop graft-versus-host disease, even though they were not put on a regime of immunosuppressant drugs.
Perreault and his colleagues tried to figure out if following that clue could lead them to a way to differentiate which donors were likely to induce graft-versus-host and which weren't.
Dr. Fred Appelbaum, director of the clinical research division of the Fred Hutchinson Cancer Research Center in Seattle, Wash., said a variety of researchers had been trying to puzzle out why, even among well-matched donors and recipients, the risk of graft-versus-host disease varies.
A team from his facility earlier identified one immune system protein, IL-10, as playing a role. Other teams focused on other proteins made by the immune system.
"It became almost undoable because there are so many to look at,'' said Appelbaum, who was not involved in this study.
"His (Perreault's) approach was to try and figure out: Is there a way that we can do a global assessment, that we take into account all the genes and their impact on cells?''
The Montreal team analyzed the workings of 19,000 genes from 50 bone marrow donors, looking for discernible patterns of over- or under-production of important immune system proteins. They found that by looking at the activities of 17 genes, they could identify dangerous and non-dangerous donors.
Perreault said the group will now test the theory in a larger group of donors, to see if their tool really works. The gene activities of several hundred donors will be studied for this follow-up research.
Appelbaum said if corroborated, the work will provide an important predictive tool for doctors planning bone marrow transplants and treating recipients after the procedure.
"In those cases where you have multiple donors, you could use it to select one donor over another,'' he said. " In those cases where you don't have that option ... you might be able to use it to fine tune the amount of immune suppression you give (recipients).''
"So that if someone is a dangerous donor, you'd use higher doses of post-transplant immune suppression and if someone appears to be a safe donor, you might be able to more rapidly taper the immune suppression so that they're at less risk of development of infections and other complications.''
And if the solid organ rejection can be predicted in the same manner, in future recipients of donated livers and kidneys would be tested to see whether they are likely to reject _ and their drug regimes would be set accordingly.
"We really anticipate that the same genes will be predictive of solid organ rejection,'' Perreault said.
The research was funded by Genome Quebec, Genome Canada, the Dana Foundation and the Health Research Fund of Quebec.
