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Possible treatment target found for main cause of severe liver disease in kids
Date:11/8/2011

had been linked consistently to the biochemical processes that cause biliary injury. Th cytokines, also referred to as T-helper cells, are part of the immune system. They send molecular signals to help initiate and maximize the body's immune system response. In biliary atresia, that response can go into overdrive and become too aggressive, piling on damage to the bile ducts and the liver.

Despite the prevalence of Th1 detection in children with the disease, there have been reports that some biliary atresia patients exhibit low levels of Th1. This led Bezerra and his colleagues to look for Th1-independent drivers.

They tested their hypothesis with genetically modified newborn mice that lack the ability to mount a Th1-modulated immune response. The mice were infected with rhesus rotavirus Type A, which can cause severe inflammation of the bile ducts if infections occur soon after birth. This prompted an almost immediate and robust immune response involving Th2 cytokines.

The mice developed damaged bile ducts, duct obstructions within seven days and then full atresia (blockage) shortly thereafter. The researchers then depleted a Th2 molecule known as Interleukin 13 and noted a reduction in tissue infiltration by immune cells. It also maintained the integrity of bile duct tissues and prevented obstructions from occurring.

Bezerra examined the blood of children with biliary atresia and found that some of them exhibit high levels of Th2 cytokines. This, coupled with the current study findings, demonstrate "a compatibility between Th2 and the onset of biliary atresia, and suggest that patient subgrouping in future clinical trials should account for differences in Th2 status," he said.

The current study was funded in part by grants from the National Institutes of Health and the Digestive Disease Research Core Center in Cincinnati. It follows a study from Bezerra and colleagues published Sept. 29 in Science Translational Medici
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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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