Tricking the Immune System

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How desensitization could change the landscape of food allergies

For my eighth birthday party, my parents hired a magician, one whom I had first seen while hospitalized for complications of food allergies. As he pulled rabbits from hats, found coins hidden in our ears and produced yards of colorful fabric from his sleeves, my friends and I marveled at his tricks.

Yet the real magic that day was orchestrating a safe birthday party for me—no small feat with my allergies to milk, eggs and nuts. Outside the house, the world seemed full of frustration and danger. From birthdays to school events to restaurants, there were many times growing up that I wished I could wave a magic wand and be rid of my allergies for good.

Because of these early experiences, I became fascinated years later by the search for a cure for food allergies. Immunotherapy—the process of gradually administering an allergen to patients to teach their immune systems not to react—seemed to offer an almost magical path to a life without food allergies.

The goal of immunotherapy is to alter the immune system’s response to an allergen so you will no longer have severe reactions or perhaps you will even be able to eat it regularly. It involves purposeful exposure to the culprit food in increasing doses over months or years to slowly diminish your body’s errant response.

Wesley Burks, MD, an expert in pediatric allergy, describes how this process works for patients in his clinical trials. “We give a child extremely small amounts of the food they are allergic to over time so that their immune system will develop a different immune response to the food,” he explains. “In doing this, the child will be able to eventually tolerate the food without allergic symptoms as long as they are taking the daily treatment.”

This process of successfully reducing allergic reactions, known as desensitization, makes life much safer and easier, as it can reduce the risk of a severe anaphylactic reaction. Beyond desensitization, the ultimate goal of this therapy is tolerance: allowing you to enjoy the allergen as part of your diet—something akin to a permanent cure.

One of the first large-scale demonstrations of these strategies was a landmark clinical trial, published in the New England Journal of Medicine in 2012. A team of researchers—led by Burks—demonstrated that egg allergy could be successfully treated with oral immunotherapy, desensitizing most patients and even allowing some patients to eat eggs on a regular basis.

“The studies on desensitization have allowed us to better understand the immune response to immunotherapy strategies,” says Burks, who is chairman of the Department of Pediatrics at University of North Carolina School of Medicine and physician-in-chief of North Carolina Children’s Hospital. “They also show that we may, in fact, be able to create a long-term effect for some of these patients.”

Researchers have now examined several different forms of immunotherapy, explains Burks, including allergen exposure across the skin (epicutaneous immunotherapy), drops of allergen extracts placed under the tongue (sublingual immunotherapy) and ingestion of the allergen itself (oral immunotherapy). So far, these methods have been used with variable success to treat milk, egg and peanut allergies. Oral immunotherapy—eating escalating amounts of the allergen—seems to hold the most promise for inducing permanent tolerance.

“Each of these therapies has a differing efficacy and potential for allergic side effects,” says Burks. “In general, oral immunotherapy has had the strongest effect but the most side effects. There does not appear to be a difference in one type of immunotherapy with differing food allergens.”

How It Works

True allergic reactions are caused by antibodies that react to the food protein and activate a dangerous immune response. The reason immunotherapy works is not well understood but is thought to be related to activation of cells that suppress this response. By slowly increasing exposure to the allergen, the desensitization process successfully turns off allergic reactions in many patients.

“The leading hypothesis,” says Burks, “is that the primary effect of desensitization is on forms of the IgG receptors,” a type of antibody found bound to immune cells that are involved in allergic reactions. There are many other secondary effects, explains Burks, on other aspects of the immune system, such as T cells, that help to reduce allergic reactions over time.

Surprisingly, the notion of treating allergies in this manner is more than 100 years old. In 1911, the British scientist Leonard Noon developed a treatment for hay fever consisting of a series of injections of small amounts of grass pollen. Inspired by the success of vaccines, Noon hoped his patients would develop an “active immunity” to the pollen, thus curing their allergy.

In his laboratory, Noon prepared various pollen extracts to test his hypothesis. First, he sprinkled the extract into patients’ eyes to study their reactions. He then injected them with the pollen extract over several weeks in increasing amounts and found that he could successfully reduce their sensitivity. Noon’s 1911 study was the first successful example of immunotherapy, using gradual exposure to the allergen in order to coax the patient’s immune system into tolerating the foreign substance.

For a long time after Noon’s experiments, the prospect of immunotherapy for food allergies was scuttled by the risk of severe reactions. The unpleasant symptoms of hay fever that Noon observed were nothing compared to life-threatening anaphylaxis caused by food allergies. Unfortunately, even today, says Burks, “we would not recommend giving any of these therapies outside of a clinical trial. There are too many potential allergic side effects.”

Another significant problem with immunotherapy is that the effect is variable between different patients and often disappears once the exposure is stopped. “We cannot identify at this time the type of patients who would most benefit from these therapies,” explains Burks. Although immunotherapy is highly successful in initial desensitization, it is not clear whether it truly represents a cure. If patients do not continue to have regular exposure to the allergen, the benefits of the process are often lost.

More to Learn

For many, the possibility of fewer reactions, or perhaps even a cure, is worth the risks and allergists are continuing to invent and refine new strategies for desensitization. In some experimental research, scientists are also using additional medications that suppress the immune system or even genetically engineering food proteins that can trick the body’s immune cells. Their goal is to make the process safer, more predictable and more effective. However, there is still a great deal to learn about how well these treatments work, what effect they have on the immune system and what is the best and safest way to attempt immunotherapy.

There is, unfortunately, no magic cure for food allergies. At this time, explains Burks, “there is no good evidence of long-lasting cure from these therapies. The best outcome we have observed is that some of the treated patients experience a long-term effect where they can consume the food safely on a regular basis.” It’s important to be aware that immunotherapy has significant risks and limitations and the only true treatment remains careful avoidance of the allergen.

In the future, says Burks, there will be many more experiments examining the different types of immunotherapy, “including studies aimed at developing a treatment that will be long-lasting and not just produce desensitization. We are currently conducting studies in animal models of food allergy looking at different prototypes of immunotherapy and also examining the mechanisms of immunotherapy.”

With this type of innovative research in immunotherapy, our understanding of food allergies is improving rapidly and it seems a cure may at least be on the horizon.

Joshua Feblowitz, MD, lives in Boston and is specializing in emergency medicine.

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