Fear and Allergies in the Lunchroom

It is hard to fathom how the joys of childhood—a peanut-butter sandwich, a warm chocolate-chip cookie, a cold glass of milk—can send a tiny body into battle mode. How just one bite can make the throat itch, the lips swell, the stomach clench in agony. How an immune system, exquisitely designed to protect us against bacteria and viruses, can perceive healthful nutrients as enemies of state. Bryan Bunning, 13, and his brother, Daniel, 11, of Lake Forest, Ill., know what it's like. Bryan was 6 months old when his body revolted against a sip of milk-based formula. "His lips blew up and his eyes went back in his head," says his mother, Denise. The boys share a list of verboten foods between them: eggs, tree nuts (including cashews, walnuts, almonds, hazelnuts), milk and shellfish. In March, Daniel was diagnosed with an allergy-related disorder of the esophagus that left him able to eat only apples and bacon. Now he gets most of his nutrients through a feeding tube. "It's really hard going to parties. You watch all your friends eat what they say are amazing foods, like ice- cream cake," says Daniel. "They're, like, 'Daniel, it's really good.' I say, 'I can't, I have food allergies'."

Nobody knows precisely what causes food allergies. A combination of genes—allergies run in families—and environment clearly play a role. The cascade of events begins when an allergy-prone person encounters a substance like pollen or peanut. The body sees it as trouble and launches phase one of its offensive: the production of antibodies called IgE (immunoglobulin E). These molecules attach themselves to "mast" cells, which line the lungs, intestines, skin, mouth, nose and sinuses. The next time the person encounters the pollen or peanut, the mast cells are primed for warfare, sending out powerful chemicals, like histamine, which lead to those nasty allergic symptoms—wheezing, stomach cramps, itching, stuffiness, swelling and hives. In rare instances, when the response to an allergen is sudden and severe, the airways can shut down completely and blood pressure can plummet, leading to anaphylaxis. Without immediate treatment with epinephrine, a hormone that opens the breathing passages and increases heart function, anaphylactic shock can kill.

Intriguing new research into the cause of allergies lends credence to the hygiene hypothesis. Studies have shown that children who grow up on farms, where they are in constant contact with dirt and animals, are less likely to develop allergies. Canadian research published earlier this month also suggests they're at less risk of asthma. At Duke, scientists have examined the phenomenon at the molecular level by comparing the immune systems of wild, parasite- and infection-ridden rodents with their cleaner, lab-raised cousins. In a setup intended to simulate an allergic response, researchers put the animals' immune cells in a petri dish, then challenged them with a plant protein—a known immune-system stimulus—to see how the cells reacted. Last year they published their findings: the lab rodents had a much higher immune response than their wild relatives did. Their immune systems were working overtime. And the wild animals, who were unfazed by the stimulus, showed higher levels of antibodies in their blood, suggesting that they'd already battled far greater enemies and couldn't be bothered by the small stuff. "We think the wild ones probably wouldn't get an allergy," says lead investigator William Parker. "They just don't have time to mess with a pollen grain when they're fighting off some horrible parasitic liver worm." Parasites, Parker says, might ultimately help scientists find a cure. Studies have shown that patients with irritable bowel syndrome, a digestive and immune disorder, may improve if they're exposed to a pig parasite, the porcine whipworm. Parker is eager to see if similar, controlled exposure can "stimulate the immune system in a good way" in allergic kids. No one's done the research—yet—but in theory, he says, it's "highly promising."

Fixing the immune system, so that it learns to distinguish good from bad without error 100 percent of the time, is every immunologist's dream. Unfortunately, researchers still don't know enough to make that dream a reality. But what if the system could be desensitized, so kids became more tolerant of the very foods they are allergic to? The approach, called immunotherapy, is already standard practice for seasonal allergies like hay fever. Patients receive allergy shots containing small but increasing amounts of the problematic substances—weeds or tree pollen—so the immune system gradually becomes used to the allergens. Researchers have tried immunotherapy by injection for food allergies, but it's unsafe; patients may develop hives or other troubling reactions. Now scientists led by Dr. Wesley Burks at Duke are carefully testing the immunotherapeutic approach by mouth rather than needle, and they're beginning to see promising results. In a small study published in The Journal of Allergy and Clinical Immunology in January, Burks and Dr. Stacie Jones at Arkansas Children's Hospital reported that immunotherapy helped children with egg allergies tame their allergic reactions. After two years of ingesting small but increasing amounts of egg powder, most of the children could eat the equivalent of two eggs without any adverse reaction. Kids in a similar study, published this month in the journal Allergy, also developed a tolerance to eggs—although that effect disappeared after they stopped eating the powder.

Burks is using the same approach with peanuts, giving peanut-allergic children increasing amounts of a special flour with small amounts of peanut proteins. The first dose is the equivalent of about 1/1000th of a peanut; slowly, the kids have been working up to a peanut a day. Early in the trial, participant Noah Schaffer, 7, threw up after eating just 25 milligrams of peanut protein—equal to about 1/12 of a peanut. But at a food challenge last May, he ate the equivalent of 13 peanuts without any bad reaction. Burks says the results don't mean that Noah can now knowingly indulge in a Snickers bar—far from it. But his new tolerance could protect him if he accidentally had a bite of one. His mom, Robyn Smith, says she no longer worries that something terrible will happen. "That fear has been totally removed," she says.

Burks's peanut flour is a precursor to what researchers hope might one day be a peanut vaccine. Together, Burks and Sampson have developed a substance that looks like a peanut but contains proteins engineered to be less potent—and thus less likely to trigger an allergic response in patients. So far, the compound has been tested successfully in mice. "If it works in people," says Sampson, "we hope to shut off the allergic response."