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Scientists link immune system's natural killer cells to infant liver disease
Date:7/22/2009

CINCINNATI Scientists have linked an overactive response by one of the immune system's key weapons against infection natural killer, or NK, cells to the onset of biliary atresia in infants, a disease where blocked bile ducts can cause severe liver damage and death.

Researchers at Cincinnati Children's Hospital Medical Center also report that blocking a gene that helps NK cells attack bile duct tissues lessens damage and may be a way to treat the most common cause of chronically progressive liver disease in children. The study, to be published in the Aug. 3 Journal of Clinical Investigation, is posted online on the journal's website.

"Our findings underscore the developing immune system's role in causing injury to bile ducts soon after birth, and they have implications for developing new therapies to block the disease by targeting certain cells or pro-inflammatory circuits," said Jorge A. Bezerra, M.D., the study's senior investigator and research director of the Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's.

"The next steps for translating these findings into clinical application would include pre-clinical trials of biologics to halt disease progression by blocking the Nkg2d receptor and depleting NK cells at the time biliary atresia is diagnosed," he added.

Very little is known about the cause of biliary atresia, although it has been traced to the immune system responding to an infection in the liver and bile ducts. Surface tissues inside the bile ducts are damaged, which in turn allows inflammatory cells to block the duct and the ongoing accumulation of fibrotic tissue. Biliary atresia affects about one in every 15,000 babies.

The current frontline treatment is surgery to remove and replace obstructed bile ducts with sections of the child's intestine. Without surgery, bile cannot enter the intestines to aid digestion, and instead backs up into and damages the liver.
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert  

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