Immune changes can cause peanut allergy remission
The potential of new, more focused allergy treatments is now possible thanks to the identification of the key immunological changes that allow the remission of peanut allergy in children.
For the first time, researchers discovered that particular gene networks are rewired to drive the transition from peanut allergy to clinical remission after combination treatment of a probiotic and peanut oral immunotherapy.
The research, led by the Murdoch Children’s Research Institute (MCRI) and the Telethon Kids Institute, discovered that network reprogramming effectively shuts down the allergic immune response that causes a food allergy. The study was published in the journal Allergy.
Murdoch Children’s Professor Mimi Tang, who led the study, said it was the first to identify the complex gene-to-gene communication and connectivity underlying clinical remission of peanut allergy.
“The immunological changes leading to remission of peanut allergy were largely unknown,” she said. Previous studies had mostly focused on examining the levels of gene expression, without also exploring how genes interact with each other. But genes don’t work in isolation; instead, biological responses are controlled by large numbers of genes communicating with each other, so it made sense to look 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. These same changes were also seen when we compared gene networks before and after immunotherapy in the children who achieved remission following immunotherapy.”
62 Melbourne-based children with peanut allergies, ages 1 to 10, participated in the randomized controlled experiment. They were either given a placebo or a probiotic treatment that included oral immunotherapy (the progressive introduction of the allergenic food). After 18 months of treatment, 74% of patients receiving the combo therapy had remission, compared to 4% of those receiving a placebo.
PRT120, a lead candidate from Prota Therapeutics, an Australian biotech firm focusing on commercializing its breakthrough allergy immunotherapy treatment for kids with life-threatening peanut allergies, was the peanut oral immunotherapy combined with the probiotic in the study.
The team led by Professor Tang recently demonstrated in different research that two treatments, peanut oral immunotherapy alone and a combination of probiotics and peanut immunotherapy, were both very successful in causing remission and desensitization. Remission was obtained in around half of the treated children, allowing them to stop receiving medication and start eating peanuts without risk.
Murdoch Children’s Dr. Sarah Ashley said while oral immunotherapy could successfully induce desensitization and remission, desensitization often waned after treatment ended or even during ongoing maintenance dosing.
“Certain changes in the allergen-specific immune cells, called Th2 cells, are critical to achieving lasting remission,” she said. Th2 cells are essential for generating allergen-specific antibodies and the development of food allergies. We found that the Th2 signaling that drives allergy is ‘turned off’ in children in remission.”
Food allergy is a global public health concern, affecting 10% of infants and 5-8% of children.
Telethon Kids Institute’s Dr. Anya Jones said because there was no cure for food allergies, management relied on avoidance of the allergenic food, resulting in reduced quality of life.
“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,” she said.
Ju Lee Ng’s daughter Stella, 9, was diagnosed with a peanut allergy at 18 months of age after breaking out in hives from a meal containing traces of the nut.
But Ju Lee said after taking part in a Murdoch Children’s allergy trial, Stella had been in clinical remission for almost four years and now eats peanuts regularly.
“Stella’s quality of life has improved considerably since the trial,” she said. Her level of anxiety has reduced dramatically and she has the freedom to enjoy different types of food. Stella no longer has to always check food labels for peanuts and brief her teachers or friends’ parents about her allergy. She can now dig in and enjoy a bag of peanut M&Ms.
“We previously had to avoid travel to countries that use lots of peanuts in the food, including Malaysia, where my husband and I are from. Shortly after Stella achieved remission we were so excited to be able to travel on a family holiday to Thailand. We tried local dishes and enjoyed an amazing holiday without the stress that Stella could have an allergic reaction.”
Ju Lee said it was reassuring to learn that new treatments could be developed off the back of the latest study results by the Murdoch Children’s.
“This research will give a lot of hope to families who have children with a peanut allergy,” she said. We hope other families can experience the same sense of comfort we now have with a child who can eat peanuts freely without fear of a reaction.”
Reference: “Remission of peanut allergy is associated with rewiring of allergen-driven T helper 2-related gene networks” by Sarah E. Ashley, Anya C. Jones, Denise Anderson, Patrick G. Holt, Anthony Bosco and Mimi L. K. Tang, 25 May 2022, Allergy.
Researchers from the University of Melbourne, The Royal Children’s Hospital, and The University of Western Australia also contributed to the study.
The study was funded by the National Health and Medical Research Council Australia.