Mixing Up the Immune System

Transplanting bone marrow along with kidneys reduces the risk of organ rejection.

Post-op progress: Kidney-transplant patients whose immune systems were primed with donor bone marrow didn't need long-term treatment with immune-suppressing drugs. Credit: AJPhoto / Photo Researchers, Inc.

By performing bone-marrow transplants along with kidney transplants, doctors in Boston were better able to trick recipients' immune systems into accepting the new organs as if they were their own.

Even though the patients received donor kidneys that weren't a good match, most of them were successfully weaned off of immune-suppressing drugs about a year after their transplants. Normally, patients have to take the drugs, which can have serious side effects, for the rest of their lives.

"It's groundbreaking work," says John C. Magee, director of the Kidney Transplant Program at the University of Michigan, who was not involved in the study. "They've shown that you can reeducate the immune system."

The technique could be applied to other kinds of transplants and used in the treatment of autoimmune diseases, says Megan Sykes, one of many researchers who carried out the work at Massachusetts General Hospital. Sykes is the associate director of the hospital's Transplantation Biology Research Center.

The team has been working for about 20 years to outsmart the immune system by inducing tolerance to a donor organ. In this study, reported in this week's issue of the New England Journal of Medicine, the scientists transplanted bone marrow along with a mismatched kidney, giving patients a kind of hybrid immune system that blended elements of both the donor and the recipient.

Four out of five patients who received bone-marrow transplants in conjunction with kidney transplants didn't need long-term treatment with immune-suppressing drugs. The technique was not successful for the fifth patient, however: his body rejected the donor kidney. He was given a second--and successful--transplant according to conventional protocol.

Doctors try to match people with similar versions of the genes that play a crucial role in immune reactions to foreign tissue. This genetic region is known as the human leucocyte antigen (HLA) complex. But finding a good match isn't always possible, so doctors often use a mismatched kidney and put the patient on immunosuppressive drugs to reduce the risk of rejection. The patients in the study, whose ages ranged from 22 to 46, were all suffering from advanced kidney disease and were unable to find living donors who were a very good tissue match. They received kidneys from family members who were HLA mismatched.

Before the surgery, the transplant team gave the patients drugs to deplete their bone marrow and suppress their immune response. After receiving new kidneys and then an intravenous infusion of bone marrow from their donors, the patients were kept in a relatively sterile environment to reduce their chance of infection, and to allow the bone marrow to regenerate and produce new immune cells that wouldn't attack the donor kidney.

In the months after their transplants, the patients in the study were treated with immunosuppressive drugs, but four out of five of them were able to discontinue those drugs between 9 and 14 months after surgery, and their new kidneys have been functioning well in the years since.

"I think it's quite exciting," Magee says. "It shows what's possible."

The researchers' approach could make transplants more feasible for people whose immune systems are already compromised by conditions like HIV, according to Yasir Qazi, medical director of the kidney and pancreas transplant program at the University of Southern California. (Qazi was not involved in the work.) Sykes says that the approach could potentially be used to treat autoimmune diseases such as type 1 diabetes. "It could have huge benefits," she says.

Although immunosuppressive drugs have revolutionized transplant medicine, they can increase the risk of cancer and heart disease. "Immunosuppression is great, because it makes kidneys work, but it's bad because it has lots of side effects," Magee says. "Some people say that in many ways, you're trading one disease for another. You still have to take lots of medicine and see a doctor."

The protocol developed by Sykes and her colleagues initially requires heavier drug treatment than that required with the standard kidney-transplant procedure, to allow the recipient's body to accept donated bone marrow as well as a donated kidney. But, she points out, the patient is only on the drugs for a limited time.

http://www.technologyreview.com/Biotech/20106/