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Study points to key genetic driver of severe allergic asthma
Date:8/29/2010

CINCINNATI Scientists have identified a genetic basis for determining the severity of allergic asthma in experimental models of the disease.

The study may help in the search for future therapeutic strategies to fight a growing medical problem that currently lacks effective treatments, researchers from Cincinnati Children's Hospital Medical Center report in the Aug. 29 Nature Immunology.

The prevalence of asthma has been increasing in recent years, according to Marsha Wills-Karp, Ph.D., director of the division of Immunobiology at Cincinnati Children's and the study's senior investigator. The disease can be triggered in susceptible people by a variety of environmental contaminants such as cigarette smoke, allergens and airborne pollution.

Dr. Wills-Karp's research team has found a molecular tipping point that upsets a delicate balance between underlying mild disease and more severe asthma. They identify the pro-inflammatory protein, interleukin-17 (IL-17A), as the chief culprit behind severe asthma-like symptoms in mice.

"This study suggests that at some point it may be possible to treat or prevent severe forms of asthma by inhibiting pathways that drive the production of IL-17A," Dr. Wills-Karp said.

The disease process appears to begin when airway exposure to environmental allergens causes dysfunctional regulation of a gene called complement factor 3 (C3), which works through a part of the immune system called the complement activation cascade. This leads to overzealous production of IL-17A by airway cells and sets off what the scientists describe as an "amplification loop," when IL-17A in turn induces more C3 production at the airway surface.

The amplification loop perpetuates increasing inflammatory responses involving irregular T helper cells, other interleukin proteins (IL-13 and IL-23), as well as airway hyper-responsiveness and airflow obstruction.

Previous studies have shown the pr
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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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