Key Signaling Switch Identified in Allergic Disease

A research team has identified a key enzyme responsible for triggering a chain of events that results in allergic reaction, according to new study findings published online this week in Nature Immunology.

The work by researchers from Virginia Commonwealth University, the Hospital for Special Surgery and Weill Cornell Medical College in New York sets the stage for development of new strategies and target therapies that control allergic disease – the sixth leading cause of chronic disease in the United States.

Allergic diseases such as asthma and hay fever are problematic for about 30 percent of the population in the developed world. Researchers have developed various treatments to control allergy, but no cure has been found.

The team has demonstrated, for the first time, the role of a proteolytic enzyme called ADAM10 that releases a major allergy regulatory protein from the surface of cells and thereby promotes a stronger allergic response. The identification of drugs that inhibit ADAM10’s ability to release this molecule could revolutionize treatment of asthma and allergic disease.

“Our research, for the first time, may represent a treatment strategy to prevent, rather than simply control IgE-mediated allergy,” said Daniel Conrad, Ph.D., a professor in VCU’s Department of Microbiology and Immunology. Conrad directed the research conducted at VCU. IgE is an antibody known to trigger Type I allergic disease.

“Understanding ADAM10’s role in allergic disease makes it a potential target for the design of drugs to treat asthma and allergic disease,” he said.

According to Conrad, the outcome of allergic disease can be modulated by high levels of the regulatory protein, known as CD23, which ultimately results in a decreased production of IgE. He said that when the regulatory protein is released from the cell surface by ADAM10 there is an increase in the production of IgE and therefore, increased allergy.

“These exciting results extend the known functions of ADAMs in development and disease. We hope our results will stimulate new research into how to block or activate the function of ADAMs involved in human disease, including allergic response, cancer and rheumatoid arthritis,” said Carl P. Blobel, M.D., Ph.D, chair of the Arthritis and Tissue Degeneration Program at the Hospital for Special Surgery, and professor of Medicine and of Physiology and Biophysics at Weill Cornell Medical College. Blobel directed the research conducted at Weill Cornell.

According to Blobel, in addition to the critical role of ADAM10 in allergic disease through processing of CD23, ADAMs are also key molecules in cancer and rheumatoid arthritis. For example, he said, ADAMs are essential for activating the epidermal growth factor receptor, an established target for the treatment of cancers, such as colon cancer. Moreover, ADAMs release tumor necrosis factor alpha, currently the major target for treatment of rheumatoid arthritis.

Since the 1970s Conrad has been investigating the basic mechanism involved in allergic disease. Blobel has been investigating ADAM proteases since their discovery in the early 1990s.

Source: Virginia Commonwealth University

Related stories:

Scientist to bare his DNA
Here's some personal information about Misha Angrist: His blood pressure is 104 over 65. He weighs 173 pounds, has fought anxiety and depression and is very allergic to cats.
New treatment desensitizes children's allergies
One M&M, swallowed whole, and little Noelle's skin turned as red as a Cortland apple. A month later, after eating soy ice cream, the 2-year-old turned colors again and started drooling, prompting her mother to inject a syringe full of epinephrine into the child's leg.
Drinking milk to ease milk allergy?
Giving children with milk allergies increasingly higher doses of milk over time may ease, and even help them completely overcome, their allergic reactions, according to the results of a study led by the Johns Hopkins Children's Center and conducted jointly with Duke University.
Fishy diet in early infancy cuts eczema risk
An infant diet that includes fish before the age of 9 months curbs the risk of developing eczema, indicates research published ahead of print in the Archives of Disease in Childhood.
Pollen Alert!
When you stroll through your front door in the morning, does the yellow haze coating the porch send you leaping back into the house? Can the mere word "pollen" make you start to sniffle, sneeze and reach for the tissue to blow your nose?
Rodent studies suggest mother's diet can affect genes and offspring's risk of allergic asthma
A pregnant mouse's diet can induce epigenetic changes that increase the risk her offspring will develop allergic asthma, according to researchers at National Jewish Health and Duke University Medical Center. Pregnant mice that consumed diets high in supplements containing methyl-donors, such as folic acid, had offspring with more severe allergic airway disease than offspring from mice that consumed diets low in methyl-containing foods. The results of the study are being published Sept. 18, 2008, in the online version of the Journal of Clinical Investigation and will appear in the October print issue.
Most vaccine-allergic children can still be safely vaccinated, experts say
With close monitoring and a few standard precautions, nearly all children with known or suspected vaccine allergies can be safely immunized, according to a team of vaccine safety experts led by the Johns Hopkins Children's Center. Writing in the September issue of Pediatrics, the multicenter research team offers pediatricians a step-by-step tool for quickly identifying children with allergic reactions to vaccines, and a much-needed guide, they say, to safely immunize those who are allergic.
Chemists move closer toward developing safer, fully-synthetic form of heparin
Chemists are reporting a major advance toward developing a safer, fully-synthetic version of heparin, the widely used blood thinner now produced from pig intestines. The U. S. Food and Drug Administration last spring linked contaminated batches of the animal-based product, imported from China, to more than 80 deaths and hundreds of allergic reactions among patients exposed to the drug for kidney dialysis and other conditions.

News discussion:

Medicine & Health news