In search of general theories

Peanut allergy therapy produces EPIGENETIC changes in immune cells

03.04.2014 09:46

NATURE MEDICINE | SPOONFUL OF MEDICINE

 

 | Posted by Nicholette Zeliadt | Category: 

Earlier this week, news that six months of exposure therapy to peanuts enabled almost 100 children with an allergy to this food to eat the equivalent of ten peanuts stirred a lot of optimism. It was just one of manystudies showing that some patients with severe peanut allergies can actually gain the ability to consume small amounts of the food by eating a little bit of this nut each day, gradually increasing the dose over several months.

Scientists may now have a better handle on how this ability to shrug off peanut allergy forms, and why some individuals respond to the treatment while others do not. A study published today in the Journal of Allergy and Clinical Immunology reports that the immune cells of some patients with peanut allergies who became tolerant to peanuts after exposure therapy showed DNA modifications thought to perhaps have a role in defending against allergies. “By understanding what changes occur,” says lead author Kari Nadeau, an immunologist at the Stanford School of Medicine in California, “we can identify targets for new therapy and biomarkers by which we can decide whether or not to keep treating a patient.”

The study involved 43 children and adults allergic to the nut, 20 of whom completed two years of exposure therapy and developed the ability to tolerate as much as a 4-gram serving of peanut protein—roughly the equivalent of half a tablespoon of peanut butter, according to Nadeau. The researchers then took the participants off the therapy and asked them to avoid peanuts entirely.

Three months after the patients stopped taking the therapy, the researchers administered a small dose of peanut protein and found that 13 of the 20 participants developed allergic reactions, whereas seven remained peanut-tolerant. Compared with participants who regained their allergies, the individuals capable of eating the food without a problem had roughly twice as many peanut-specific regulatory T cells, a type of immune cell that helps to dampen allergic responses.

Furthermore, in people who were desensitized to peanuts, the FOXP3 gene—which is important for regulatory T cells’ immune suppressing ability—had fewer chemical tags known as methyl groups attached to it. These tags, known as epigenetic modifications, are known to modify the action of a gene. In the future, Nadeau says, one might potentially gauge patients’ responsiveness to peanut therapy based on how few of these epigenetic modifications they have.

However, further studies are needed to precisely determine the mechanisms by which exposure therapy induces tolerance. “This is a good preliminary study,” says Wesley Burks, an allergy specialist at the University of North Carolina School of Medicine in Chapel Hill who has conducted clinical trials of exposure therapies for peanuts and other foods that can trigger allergies. But, he noted that the sample size was very small and, given the large degree of variability among humans, it would be important to verify the findings in future studies involving more subjects. Nevertheless, he called the results “encouraging” because they show that some individuals can maintain peanut tolerance for months after ending this type of immunotherapy. So far, he says, preliminary tests have suggested that many people can’t.

Doctors add that peanut exposure therapy has potentially dangerous side effects, and should only be used under the strict supervision of medical professionals—in other words, don’t try this at home.