On May 11, 2022, 14-year-old Jagger Shaw ate a granola bar between classes at his Nebraska school. It must have had traces of peanut. That was his last day of school. He died of anaphylaxis.
Past research reports that giving peanut oral immunotherapy to highly peanut-allergic children ages 1 to 3 years safely desensitized most of them to peanut. The mechanism that induces remission, however, has been elusive. Now, researchers at the Murdoch Children’s Research Institute in Australia have identified the key immunological changes that facilitate the remission of peanut allergy in children.
Peanut allergy affects about 2% of children in the United States, or nearly 1.5 million individuals ages 17 years and younger. The risk of a life-threatening allergic reaction to accidentally eaten peanut is significant for these children.
The research shows, for the first-time, that specific gene networks are rewired to drive the transition from peanut allergy to clinical remission, following a combination treatment of a probiotic and peanut oral immunotherapy.
“The immunological changes leading to remission of peanut allergy were largely unknown,” says study leader Mimi Tang, a professor at the institute, in a statement. Previous studies focused on the levels of gene expression, without exploring how genes interact with each other. Genes don’t work in isolation, however, so the team looked at these interactions more closely.
“What we found was profound differences in network connectivity patterns between children who were allergic and those who were in remission,” says Tang. “These same changes were also seen when we compared gene networks before and after immunotherapy in the children who achieved remission following immunotherapy.”
Dr. Sarah Ashley, Tang’s colleague, explains that while oral immunotherapy could successfully induce desensitization and remission, the desirable effect often waned after treatment ended, sometimes during ongoing maintenance dosing.
“Certain changes in the allergen-specific immune cells, called Th2 cells, are critical to achieving lasting remission,” she says. “Th2 cells are essential for generating allergen-specific antibodies and the development of food allergy. We found that the Th2 signaling that drives allergy is ‘turned off’ in children in remission. Understanding the complex immune processes that support remission will provide greater insight into key drivers of treatment success and potentially identify novel targets for more effective treatments that deliver long-term solutions for patients.”
Quality of life can improve considerably for children in remission. Their anxiety can be reduced substantially, and they can enjoy different types of food. Teachers and friends’ parents do not have to be briefed about their allergy.
“This research will give a lot of hope to families who have children with a peanut allergy. We hope other families can experience the same sense of comfort we now have with a child who can eat peanut freely without fear of a reaction,” comments Ju Lee Ng, whose 9-year-old daughter Stella took part in the trial.
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