Immunotherapy Treats Kids Allergic to Peanuts by Reprogramming Their DNA

The peanut allergy is an increasingly common disorder, and peanuts affect more food-allergic children in the U.S. than any other food type, according to a 2011 study published in Pediatrics.

However, there be a way to outdo Mr. Peanut. Researchers at the Cambridge University Hospitals NHS Foundation Trustl have found that six months of oral immunotherapy treatment (OIT), or eating small amounts of peanut protein under medical supervision, successfully desensitized 84 to 91 percent of children with peanut allergies to 800 mg of peanuts. This means that they could safely eat about five peanuts in one sitting. 

And that’s not the only good news for the peanut-deprived: a joint effort between researchers from Stanford University and Lucile Packard Children's Hospital has found that the success of OIT may be due to the reprogramming of children’s genes, in a process that can be confirmed with a simple blood test.

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Hair of the… Peanut

Researchers at Cambridge hoped to prove the efficacy of OIT for peanut allergies, and after studying 99 children in two different waves of OIT, they found that six months of daily ingestion of peanut protein could successfully desensitize food-allergic children.

In the first wave, 24 of 39 participants ages 7 to 16 were seen to tolerate up to 1400 mg of peanuts (about 10 peanuts). In the second wave, during which the control group was also given six months of OIT, researchers found that 54 percent of participants could tolerate 1400 mg of peanuts. When looking at a smaller amount, just 5 peanuts, 84 percent of participants in the first wave and 91 percent in the second wave displayed a high tolerance.

Why Does OIT Work?

Stanford researchers may have discovered the reasons behind the success of OIT. In a study of 20 peanut-allergic children and adults, researchers found that OIT actually alters the expression of a person's DNA.

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The study participants underwent two years of OIT, after which they stopped treatment for three months. When they were then asked to try peanuts, 13 had regained their peanut allergy, while seven remained desensitized. Using a blood test, researchers found that those seven exhibited differences in their DNA.

“We saw consistent changes at the cellular, functional and DNA level… in those subjects that had undergone oral immunotherapy and that, after three months of withdrawal, still remained unreactive to peanut protein,” said Kari Nadeau, M.D., Ph.D., an associate professor of pediatrics at the Stanford School of Medicine.

Researchers found that the success of OIT was largely dependent on the number of methyl groups that had attached themselves to a gene known as FOXP3. Methyl groups are molecules consisting of three hydrogen atoms bonded to one carbon atom, and they act as a key to gene expression.

The attachment or detachment of a methyl group to a gene—in this case, FOXP3—results in the expression or suppression of a certain gene. When DNA undergoes methylation, the attached methyl groups act as a lock on the gene, shutting down gene expression.

OIT appears to unlock FOXP3 by removing the methyl groups, undoing DNA methylation, and allowing the gene to express itself.

“We found that over the course of the study, methyl groups were ‘taken off’ the FOXP3 sites,” Nadeau said. While researchers aren’t exactly sure why de-methylation occurs, it probably relates to how immune cells called dendritic cells and T cells work together, Nadeau said.

Snacktime Safety?

While both of these studies point to the effectiveness of OIT, more studies are needed to examine if any other genes are activated by OIT and for whom these treatments work best.

“The study we present was inspired by patients, since they often ask after they are near finished with immunotherapy, 'How long will this last?'” Nadeau said. “We hope these findings will be useful to other researchers and to patients and families in the future to offer hope and promise that people are working together to try to find the best tools to measure successful outcomes for patients.”

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