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Researchers at Children's Find Promising Key to Transplant Rejection

by Mark Roth, Pittsburgh Post-Gazette, 9/17/2008

Up to half of all children who get liver transplants start to reject their organs, forcing doctors to increase their anti-rejection medication. But then, in a small fraction of those children, their immune systems are suppressed so much that they develop cancer.

Now, a new study by researchers at Children's Hospital of Pittsburgh offers hope that doctors may one day be able to fine-tune that balancing act by showing which children are more likely to reject transplanted organs.

Using an innovative screening method, scientists led by Rakesh Sindhi at Children's have shown that children who harbored a genetic mutation were more likely to reject their livers than those who didn't.

The mutation, known as a single nucleotide polymorphism, is linked to a region of the genome that controls the activity of immune system cells known as B lymphocytes.

One of the jobs of these B cells is to alert the rest of the immune system to the presence of foreign tissue, said Dr. Sindhi, director of pediatric transplant research at Children's.

When they studied liver biopsy specimens of several of the children who showed signs of rejection, Dr. Sindhi said, they found that the ones who had the genetic mutation had three times as many B lymphocytes as children without the mutation.

One of the most heartening results of the study, which appears in the current issue of the journal Gastroenterology, is that it came up with biologically meaningful results even though it had only a small sample of patients--80 children and their parents--to work with, he said.

By zeroing in on a part of the genome that governs immune activity, he said, researchers were able to analyze about 1,800 mutations shared by the children and their parents and figure out which one varied most significantly between those who rejected their livers and those who didn't.

The next step will be to try to replicate the results in a larger study involving children at several different pediatric transplant centers.

If further testing verifies the initial results, Dr. Sindhi said, it could lead to genetic screening that will allow doctors to predict who will experience rejection so they can prevent it and substantially cut the time children have to stay in the hospital after a transplant while their medications are being adjusted.

Page updated: September 22nd, 2008