FoxP3 gene expression identifies ALS disease progression in 80% of patients

Published on December 10, 2012 at 12:44 AM · No Comments

The debilitating symptoms of amyotrophic lateral sclerosis, or ALS, appear to be increased by a lack of inflammation-reducing T cells, report scientists from the Methodist Neurological Institute in an upcoming print issue of The EMBO Molecular Medicine Journal. The researchers found that expression of the gene FoxP3 -- which helps control the production of anti-inflammatory T cells -- was an indicator of disease progression in 80 percent of the patients they studied. Low FoxP3 levels were likely in patients whose ALS would develop rapidly, and vice versa.

"This is the first demonstration that regulatory T cells may be slowing disease progression, since low FoxP3 indicates a rapidly progressing disease," said Assistant Professor of Neurology Jenny Henkel, Ph.D., the study's lead author. "Levels of FoxP3 may now be used as a prognostic indicator of future disease progression and survival."

ALS is a neurodegenerative disease that slowly and inexorably causes paralysis, then death. Loss of motor control may begin in the arms or legs, or with impaired speech, and ultimately compromise breathing. ALS is sometimes called Lou Gehrig's disease. About 5 in 100,000 people are affected, and there is no known cure.

The relationship between inflammation and ALS progression is well established in humans and animal models, and many genes influencing disease development have been identified.

"While inflammation exacerbates disease in ALS patients, this inflammation is suppressed in some patients," Henkel said. "The data in our article suggest that regulatory T cells can suppress this inflammation."

In their EMBO paper, Henkel, Professor of Neurology and Chair Stanley Appel, M.D., and their team provided supportive evidence that the genes FoxP3, TGFβ, IL4, and Gata3 are involved in ALS development. But Henkel and Appel's work also suggests FoxP3 is the best indicator of disease progression when ALS symptoms first appear.

"While expression of FoxP3, TGFβ, IL4, and Gata3 may serve as indicators for latter stages of the disease, our work suggests only FoxP3 was a prognostic indicator early in the disease," Henkel said. "After following a group of ALS patients for three and a half years, low FoxP3 levels predicted a rapidly progressing disease 80 percent of the time."

Foxp3 and Gata3 are transcription factors that influence production of regulatory T cells, and Th2 "helper" T cells. TGFβ and IL-4 (interleukin 4) are anti-inflammatory cytokines.

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