April 14, 2010 --
For much of the 20th century, the peanut butter and jelly sandwich was considered a quintessential food of childhood. But that was before the rise of peanut allergies, a condition in which even the slightest exposure to peanut protein can set off a catastrophic allergic reaction. Today, labels for everything from chocolate to spaghetti sauce must include a warning if there is any chance that peanut protein may be present in the product -- and in some schools, peanut butter and jelly sandwiches are now forbidden foods.
In peanut allergy, a protein (or combination of proteins) in the peanuts triggers the immune system to create an antibody called IgE (immunoglobulin E). In turn, IgE triggers allergic reactions that can range from hives and sneezing to vomiting, diarrhea, choking, gagging, and occasionally anaphylaxis, a severe allergic reaction that can be fatal. While many foods have the capability to provoke allergic reactions, peanuts are especially problematic: not only do their symptoms tend to be more severe than most food allergies, but it only takes a tiny amount of peanut to kick off a reaction. What’s more, there’s currently no cure for peanut allergies. Once you develop an allergy, the only treatment option is complete avoidance.
Far better, of course, would be preventing a peanut allergy from developing in the first place. That’s why the World Health Organization, along with groups including Britain’s Department of Health and the American Association of Pediatrics, used to recommend not giving peanut-containing foods to children under three years old. The hope was that this would prevent children’s immune systems from becoming sensitized – that is, allergic – to the peanut proteins. But with little evidence to prove that this approach was effective, these organizations have since reduced the age of suggested avoidance to children under six months.
Despite the changes in official guidelines, however, many parents have introduced zero-tolerance policies of their own. The idea is simple -- avoid peanuts to avoid an allergic reaction. There’s just one problem: when it comes to preventing a peanut allergy from developing, this approach may be completely wrong.
That’s what the Immune Tolerance Network is trying to figure out. Over the past ten to fifteen years, the rate of peanut allergies in the United States and the United Kingdom has more than doubled. At the very least, this tells researchers that the avoidance strategy does not seem to be working – and they have begun investigating if avoidance might itself be part of the problem. Perhaps early exposure to peanuts actually helps prevent a peanut allergy from developing later in life, in the same way that growing up with a dog or cat appears to sometimes induce tolerance to their dander?
This is the question posed by the ITN’s ‘LEAP’ study (“Learning Early About Peanut Allergy”). Directed by Principal Investigator Gideon Lack, Professor of Paediatric Allergy at King’s College London, the study’s goal is to find out which strategy– exposure or avoidance -- is more successful in preventing peanut allergies in children.
Part of the inspiration for the trial’s structure came from a 2008 study, also run by Lack. He discovered that Jewish schoolchildren in the United Kingdom were almost ten times as likely to have a peanut allergy as their peers in Israel. (The study focused on Jewish schoolchildren because their shared ancestral background meant any difference in rate of peanut allergy was more likely due to environmental, rather than genetic, factors.) Lack can’t definitively pinpoint the cause for this disparity, but he suspects it might have something to do with the fact that Israeli infants and toddlers eat foods that contain peanut at far earlier ages – and in higher amounts – than their British counterparts. Lack hypothesizes that this early exposure, via the gastrointestinal tract, might prevent allergic sensitization to the peanut proteins that can cause allergic reactions – even in children with a family history of peanut allergies.
To test this hypothesis, the LEAP has study enrolled 640 high-risk children, all recruited to the study when they were between four and eleven months old. What qualifies a child as high-risk? Previous research has shown that infants who develop an allergy to eggs or an early case of severe eczema have a roughly 20 percent chance of developing a peanut allergy later on – and that, on the flip side, some 90 percent of children with a peanut allergy have a history of eczema, a dry, itchy inflammation of the upper layers of the skin.
This connection is part of what’s known as the “allergic march.” Just as eczema and egg allergies can cause a predisposition to peanut allergies, peanut allergies themselves often lead to other allergic conditions later in life – including rhino-conjunctivitis (hay fever) and asthma. This means that the LEAP study may have implications that go far beyond peanuts -- researchers hope that by figuring out how to prevent peanut allergies, they might be able to interrupt the march, preventing other allergies down the line.
Lack and his team have divided the LEAP study participants into two randomized groups: children in one group avoid peanut-containing foods until the age of five, and those in the other are given a food that contains peanuts at least three times a week (totaling about 20 grams of whole peanut a week). Along the way, the children all receive allergy testing, dietary counseling and physical examinations and will provide blood samples that will help researchers understand the differences in the way each group’s immune systems develop. When the children are five years old, they will undergo a double-blind, placebo-controlled “peanut challenge” in which they will be gradually fed increasing amounts of peanut protein, under medical supervision, to see if they’ve developed a peanut allergy.
The difference between the two groups will be used to determine which, if either, approach works best. What’s more, previously collected blood samples with each group will allow researchers to investigate how, exactly, the immune system develops an allergy toward – or tolerance for – peanut protein, information that could conceivably lead to a treatment or vaccine.
The study’s results are expected to be published in late 2014, and Lack and his team hope that its results may go beyond just shaping future guidelines. “While our goal is to learn which strategy works best in preventing peanut allergy from developing,” says Lack, “we also want to acquire a detailed understanding of the fundamental mechanisms that underpin oral tolerance to peanut and foreign proteins. Such knowledge may have far-reaching consequences in allowing us to develop new treatments for food allergy and new strategies to prevent other allergic disorders such as asthma.”
