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Genetic changes could show if peanut therapy patients in clear

Peanut alert. Fema Photo Library

Changes to the genes of people that undergo oral immunotherapy because of a peanut allergy could provide a way of testing if the treatment is working, according to findings in a new study.

Peanut allergies are the most common cause of severe and fatal allergic reactions from food and can lead to anaphylactic shock. Oral immunotherapy, which is still considered experimental, is one way of treating peanut allergy. Starting from very small doses, peanuts are given to sufferers and raised in increments to increase their tolerance.

A large clinical trial recently reported that the therapy was an effective way of treating peanut allergy in children, but given the potential severity of allergic reactions specialists warned that it was not something to be tried at home. And if regular dosing stops, there’s no guarantee that peanut tolerance will continue.

Lapsing immunity

But the findings in a new first-phase study, published in the Journal of Allergy and Clinical Immunology, potentially go a step further. The authors looked at changes that happened at a gene in the body’s regulatory T cells – immune cells that play a role in how the body responds to threats – when patients stopped immunotherapy.

While some people who stopped immunotherapy continued to show a tolerance to peanuts, others lapsed back into an allergic response. But the study suggests that genetic changes in those who remain tolerant could provide a way of monitoring patients once they finish the therapy.

The researchers, from Stanford University School of Medicine and Lucile Packard Children’s Hospital, looked at 20 children who had successfully undergone two years of oral immunotherapy. When the therapy was stopped for three months and patients given a small amount of peanut, 13 showed signs that the allergy had returned. Of the seven immune-tolerant participants, only three were still immune after six months without therapy.

The researchers compared the immune cells of children who still showed immunity, those who had lapsed and another control group of children with peanut allergies who had never received therapy. They found that the activity and expression of a gene called Foxp3, which plays a role in dealing with allergic reactions, was different in all three groups. In children who still showed low sensitivity to peanuts, the activity at the gene was lower.

These changes concern the field of epigenetics, which examines how a person’s environment or lifestyle can alter their genes.

Taking a blood test

The authors suggest that a blood test to detect this gene activity could be used to monitor allergy response and potentially free some sufferers from continuous therapy or give peace of mind about whether they were still immune tolerant. And it might give them more peace of mind about being able to eat foods that may contain peanuts.

Kari Nadeau, an associate professor of paediatrics at Stanford and lead author of the study, said: “We wanted to try to understand what biomarkers could be used to possibly predict outcome. This study allows us to move forward to confirm these in a larger study with more patients and to examine if other cells and genes are involved in the process of oral immunotherapy.

"We can’t say for sure if this is similar to going ‘ad lib’ after one completes food allergy immunotherapy but it is one step towards understanding how we can help patients understand their disease, their diagnosis, and their prognosis.”

Nadeau said a blood test that could determine changes at the gene was easy to do and could “be done with less that a teaspoon of blood”, but there were still potentially more biomarkers to find that played a part in allergy response.

Longer term protection

Johan Verhagen, from Bristol University’s School of Cellular and Molecular Medicine, said that immunotherapy aimed to induce changes in two main sets of T cells – one of which were T cells that expressed Foxp3. So changes in Foxp3 were to be expected. The main problem is that “the induced expression of Foxp3 is often not stable,” he said. But the researchers may have found patients where it was more stable. This “may indeed give them a better chance of long-term protection”.

Instead of just monitoring people who had completed therapy, the findings could be used to work out why some people remained tolerant and whether it could be replicated in others. “The main thing for them to find out now is why this happens in some but not all patients and then adapt further studies to augment this process in all patients treated, rather than just as a prediction of success,” Verhagen said.

The study also raises an interesting twist, because in epigenetics, gene changes might also be passed on to later generations. And the Stanford researchers said further studies might determine whether the success of oral immunotherapy in some patients could be passed on to their children.

“We don’t know this yet,” said Nadeau. “But some epigenetic changes can be passed on and we will be testing this in our group of patients to see how long these epigenetic changes last and if they are passed on to the next generation.”

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