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July 25, 2016

Scientists Discover Critical Element in Peanut Allergy

BRI Receives $2.9 Million from NIH to Expand Studies

Scientists at Benaroya Research Institute at Virginia Mason (BRI) recently discovered a critical pathway in peanut allergy that may extend to other food allergies. The pathway is triggered by Interleukin 33 (IL-33), a protein that helps drive the immune response that promotes allergic reactions to a substance, such as peanuts, that in most people is generally harmless.

“If we understand more about how IL-33 works, we can find the best ways to modify the pathway and hopefully stop food allergies,” says Steven F. Ziegler, PhD, BRI’s Director of Academic Affairs and the Immunology Research Program.

Dr. Ziegler and co-investigator Karen Cerosaletti, PhD, BRI Research Assistant Member and Manager of the Genotyping Core, recently received a $2.9 million grant to expand this research. Collaborators will include Virginia Mason, Stanford University Medical School and ASTHMA, Inc.

“By studying blood samples of people with peanut allergies and building model systems of food allergic responses, we’ve discovered that IL-33 is critically important throughout the development of peanut allergies and perhaps all food allergies,” says Dr. Ziegler. “It’s very exciting that currently therapies are being developed to target IL-33 in other allergic diseases.”

BRI is conducting a variety of research studies aimed at preventing and finding new treatments for potentially life-threatening food allergies. The prevalence of food allergies has increased in the past several decades and affects an estimated 5 percent of children and 3–4 percent of adults in industrialized countries.

Food allergies occur when people have an immune response to food that releases chemicals that cause sneezing; itching in the nose, eyes and ears; diarrhea and in rare cases the life-threatening reaction anaphylaxis. Currently there are few available treatments to either prevent or cure food allergies, and available medications only treat symptoms following the onset of the allergic response. Given the public health and economic impact of food allergies, there is an urgent need to identify new targets for the development of therapies for treatment as well as potential diagnostic tools to treat this debilitating condition.

Dr. Cerosaletti analyzed the human genetic samples for the “Learning Early About Peanut” (LEAP) study of the Immune Tolerance Network (ITN). This groundbreaking study demonstrated consumption of a peanut-containing snack by infants, who are at high-risk for developing peanut allergy, prevents the subsequent development of allergy. In a BRI pilot study funded by the ITN, Dr. Cerosaletti analyzed the blood of the research participants with peanut allergies to find the key genes which promote the inflammatory responses seen in allergies. These genes included Thymic stromal lymphopoietin (TSLP), IL-25 and IL-33, all of which have been studied by BRI in the past. 

“We are almost full circle in putting together the elements that explain how allergies occur,” says Dr. Ziegler. He previously identified TSLP as a new factor triggering the onset and progression of asthma and allergies. BRI principal investigator Erik Wambre, PhD, recently discovered a cell population in allergic individuals, referred to as TH2A, which initiates and promotes allergies and also responds to IL-33.  

Using model systems, Dr. Ziegler tested these proteins throughout the allergic immune response and found that IL-33 is critically important for both sensitization to allergen in the skin, as well as in the response following oral consumption. Research studies support the theory that allergies in children can develop following sensitization through the skin, leading to possible anaphylactic responses after oral consumption.

“Our new grant will allow us to replicate and expand our investigation of IL-33 and other proteins and genes in larger groups of people with food allergies, through the BRI biorepositories and research participants at Stanford, Virginia Mason and ASTHMA, Inc.,” says Dr. Cerosaletti.