Johns Hopkins scientists searching for the culprits behind peanut allergy have shortened the suspect list from 30 peanut proteins to seven, an important step towards effective treatment of a stubborn and sometimes life-threatening allergy that may affect one in every 200 children and thousands of adults.
"We still need to check this list to see if we can shorten it any further, but we're headed in the right direction," says Hugh Sampson, M.D., a Hopkins Children's Center professor of pediatrics and principal author on a report in this week's issue of the Journal of Allergy and Clinical Immunology.
Definitively fingering one or more of the proteins will open up strategic treatment options, which may also be useful against other food allergies, Sampson says.
Nearly 100 people die from all food allergies each year. Peanuts are used in a variety of food products, and some sufferers can't tolerate even proximity to peanuts, making it difficult to avoid exposures that lead to potentially dangerous allergic reactions.
To shorten the list of suspects, Hopkins scientists took advantage of the fact that patients with peanut allergy have cells known as IgE antibodies that can "cross-react" in the test tube, responding both to peanuts and to other members of the legume family like soybeans. IgE antibodies kick off many allergic reactions, triggering a chain reaction that produces symptoms like sneezing, itching, or, in more serious allergies, difficulty breathing. However, while patients' antibodies react with both peanut and soybean in the lab, most peanut allergy patients don't get sick after exposure to soybeans.
"This led us to theorize that the cross-reacting antibodies are not important to the peanut reaction, so we devised a method to remove the antibodies that were also reacting to soybean," says Sampson.
Children's Center researchers identified the peanut proteins the remaining seven antibodies bind to, and are working to pull the genes for those proteins from a library of cloned peanut DNA.
Sampson will test the proteins' links to allergic reactions in a mouse model of anaphylaxis, the life-threatening reaction induced by severe allergies that can constrict the airways in the lungs, severely lower blood pressure, and swell the tongue or throat, among other symptoms. Many peanut allergy sufferers carry an adrenalin shot with them in case of such a reaction. The only other treatment for peanut allergy is avoidance, because conventional peanut allergy shots create too much risk of a severe reaction.
Knowing the specific proteins can help scientists begin investigating several approaches for treatment.
Scientists may try injecting the genes for the proteins into allergy sufferers.
"From experiments in animals, we think this approach may have effects similar to conventional allergy shots. With one or two injections, the immune system would be stimulated in a way that reduces allergic reaction," says Sampson. The new technique doesn't appear to create the same risk as conventional shots.
Other approaches available include using drugs to block the proteins' ability to bind with antibodies, and using portions of the proteins known as epitopes to create a peanut allergy vaccine.
"Scientists can also try to genetically engineer a peanut that doesn't have these proteins," says Sampson. "This has already been done with rice in Japan, where rice allergies are more prevalent. Rice allergy isn't as severe as peanut, but it demonstrates that this approach can work."
"When we come up with a successful treatment strategy, it can be adapted to other food allergies," says Sampson. "This is a nice model for treatment of food allergy."
This research was funded by grants from the Clarissa Sosin Allergy Research Foundation, the National Institutes of Allergy and Infectious Diseases, and others.
Other study authors were Phillipe Eigenmann, M.D., of Hopkins; and George Bannon, Ph.D. and Wesley Burks, M.D., of the University of Arkansas.
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Hugh A. Sampson, M.D.
Professor of Pediatrics
The Johns Hopkins Children's Center
Division of Immunology and Allergy
PEANUT ALLERGY FACT SHEET
According to the U.S. Department of Agriculture, the United States is one of the largest commercial producer of peanuts in the world, producing more than 4 billion pounds in 1994.
The average American ingests more than 11 pounds of peanut products each year, about 55% as peanut butter and the rest in candies, baked goods and table nuts, says the U.S. Peanut Council.
Peanuts are believed to be one of the leading causes of food-allergic reactions, and one of the leading causes of fatal and near-fatal food-induced anaphylactic reactions, according to published studies by Dr. Sampson and others.
Peanuts are a legume, like peas and soybeans.
According to the American Academy of Allergy, Asthma and Immunology, two in every 100 children has a food allergy. Yet, in England, where peanut butter has only recently been introduced, 1% of 4-year-olds is reportedly allergic to peanuts.
Food allergic reactions occur when the body's immune system responds abnormally to a food protein or proteins. The body overreacts, flooding the system with histamines and other chemicals to fight off what is perceived as a threat or invader.
While physicians report that peanut allergies are on the rise, there is no epidemiologic evidence as to why. Allergists, pediatricians and emergency room physicians are reporting more cases than ever. At the Hopkins Children's Center, for example, the number of patients with peanut allergic reactions doubled from 1981 to 1991.
Dr. Sampson surmises that in today's environment, children are exposed to more peanut products (e.g. peanut butter crackers, peanut butter and jelly sandwiches and peanut butter candies) at a younger age when their immune systems are not mature enough to tolerate allergens found in peanut proteins.
Dr. Sampson recommends that parents withhold peanuts from children under 3 years old who have asthma, a family history of peanut sensitivity, or if the parents have hayfever, eczema, asthma or other food allergies.
Peanut allergy is a life-long allergy and, along with shellfish, is one of the most violent food allergies, says Dr. Sampson.
Children commonly outgrow egg, milk and soy allergies, but rarely peanut allergies, says Dr. Sampson.
Researchers at the Children's Center are trying to identify which of many peanut proteins are responsible for allergic reactions and how the immune response goes "wrong."
Allergic reactions to peanuts can include hives, swelling of the throat, difficulty breathing, vomiting and anaphylactic shock, which can be fatal if not treated.
Many children and adults with known peanut allergy should carry an injectable form of epinephrine. This version of adrenaline relaxes constricted airways for roughly 15 to 20 minutes, affording the patient valuable time to get to a hospital.
Patients with peanut allergies must read food labels and avoid dishes prepared with a utensil or cookery that was used to make a peanut-containing food.
Those with allergies must avoid not only peanuts, but foods that contain peanut products, such as enriched cocoa, Chinese dishes, brown gravies, sweets, ice cream, desserts and garnishes. Simply removing peanuts from a dish does not remove the contaminating protein.