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Mother's gift helps kidney recipients

Teen who refused anti-rejection drugs led to research

Ron Seely, Science reporter

Ten years ago at Wisconcin's University Hospital, a 16-year-old kidney transplant patient named Jamie Burris stopped taking his anti-rejection drugs because they made him sick.

Today, in the New England Journal of Medicine, a team of University transplant scientists report that they have found a way to improve the chances, by as much as 28 percent, that kidney transplant patients will survive long-term without rejecting their transplanted organ.

Their success, the scientists say, can be traced to that stubborn young man from Middleton who threw his medicine down the sink when the nurses weren't looking and ended up thriving, even without the drugs, for several years.

The work, according to University Hospital transplant surgeon Hans Sollinger, moves us closer to the day when patients can have successful transplants without the powerful drugs that are used today to suppress the immune system drugs that have unpleasant side effects and can expose the patient to deadly infections.

More immediately, Sollinger said, transplant scientists will, because of the research, have another tool to help them find the most promising organ donors.

The story of the scientists' discovery and its long genesis is an intriguing look at how science gets done. It's a story with all the elements of good drama the strange miracle of Jamie Burris, the tragic death of the young researcher who unlocked the secrets of Burris' survival, and, finally, the ultimate success of the researchers who picked up their colleague's unfinished work and pushed it through to today's publication.

Most important about the research is the finding, reported in today's article, that the presence of a particular maternal tissue type which was first discovered in Burris, who had received a kidney from his mother, Connie can help prevent the recipient's body from rejecting the transplanted organ.

When searching for a suitable donor, doctors perform tissue typing to try to find the closest match between donor and recipient. What they're looking for are matches between antigens proteins on the surface of a cell that can trigger an immune response.

In a kidney transplant, for example, the perfect match would be between a donor and a recipient who both have the same six key antigens. The fewer the antigen matches, the greater the chance that the recipient will reject the transplanted organ.

But the University team, led by Will Burlingham, a Medical School transplant scientist, found that the presence of maternal antigens, like those they found in Burris' cells, can exert a particularly powerful and positive influence.

Burlingham and his team searched the world for people who had received a kidney from a brother or sister. They ended up with a list of 205 patients who had received transplants at nine transplant centers in the United States and Netherlands. Of those transplant patients, Burlingham said, kidneys from siblings with the maternal antigen were 19 percent more likely to survive five years and 29 percent more likely to survive 10 years.

''The findings,'' Burlingham said, ''support the hypothesis that cells and antigens of the mother change the antigen-specific reactivity of the fetal immune system and promote a long-lasting form of tolerance to later antigen challenge in the adult.''

This is an area of research that has deep roots on the University campus, Burlingham said. It was former University faculty member and researcher Ray Owen who, in 1954, first reported the phenomenon of ''cellular priming,'' tolerance that comes from an offspring's exposure to the maternal immune system as a fetus and infant.

That may be what is happening here, Burlingham said. It may be what happened with Jamie Burris, a sort of additional gift that came from his mother along with her kidney.

One of the most important parts of this story, and one of the most touching, doesn't show up in today's New England Journal of Medicine. That's the story of how the late Al Grailer, a researcher in Burlingham's lab, so single-mindedly sought the scientific solution to the mystery of Jamie Burris.

After finding out about Burris and how he was doing well without anti-rejection drugs, Grailer who eventually came to be good friends with Burris started doing lab work in the early 1990s on the young man's cells to try to figure out what was happening.

Through a series of experiments that Burlingham described as ingenious, Grailer was eventually able to show that Burris was doing so well because his mother's cells were inhibiting his own body's killer cells.

That finding came on April 19, 1994, recalled Burlingham, just prior to Grailer's 38th birthday. Those results were published in the journal Transplantation, Burlingham said.

Writing about Grailer's work, Burlingham praised Grailer's search for the truth ''shining through the data from a well-done experiment.'' He called Grailer's accomplishment the scientific equivalent of a home run.

''In the lab,'' Burlingham wrote, ''we call this kind of definitive experiment a 'home run.' 'Home runs' are rare but they can change things profoundly, just like a baseball sailing over the fence can change the outcome of a ball game.''

Three years after his surprising discovery, on May 21, 1997, Grailer, who had struggled with depression for many years, killed himself. It was a stunning blow to the close-knit members of the transplant research lab, Burlingham said. Still, they continued the work that had been started by Grailer.

Today's article, Burlingham said, would not have appeared were it not for Grailer's skill as a scientist. His name appears at the top of the article as one of the authors.


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