Previous researchers had proposed a role for HHV-6 infection in LCH, but the evidence was indirect, or was questioned on grounds of possible contamination. The current study was the first to identify the virus in the cytoplasm of immune cells called lymphocytes within LCH tissues. "Our findings suggest that after the HHV-6 virus infects lymphocytes, the body mounts an abnormal immune response resulting in the overproduction of Langerhans cells seen in LCH," said Mr. Glotzbecker. The researchers confirmed the presence of the virus with in situ hybridization, a testing technique.

The virus, HHV-6, is extremely common in children and adults, but usually is cleared out of the body or neutralized by a normally functioning immune system. In fact, the researchers found evidence of the virus in 5 of 18 tissue samples from children without LCH. "Because HHV-6 infection is so prevalent, but so few children get LCH, our results suggest that the virus interacts with some underlying predisposition to the disease," said Dr. Dormans.

"We don't know what may cause a predisposition to this disease," continued Dr. Dormans, "but rethinking the cause of LCH may ultimately shift treatment away from chemotherapy toward antiviral treatments or approaches that modify the immune system." Much further research is necessary, he added, but in addition to guiding treatment, future research may lead to a simple blood test to diagnose the disease. "Such a test would be less invasive and certainly less painful for children than the tissue biopsy that we now must perform to diagnose LCH."

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Contact: Joey Marie McCool
McCool@email.chop.edu
267-426-6070
Children's Hospital of Philadelphia
8-Mar-2004