Changes in antibody levels may predict outgrowing of peanut allergies in children
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Key takeaways:
- Changes in sIgE and sIgG4 were examined to determine peanut allergy resolution.
- Changes in the levels of these antibodies over time showed which children were more likely to outgrow their peanut allergy.
A decrease in peanut specific IgE and specific IgG4 and Ara h 2 over time were associated with natural resolution of peanut allergy in a third of children by age 10 years, according to a study published in Allergy.
“Among the children that outgrew their peanut allergy, most saw their peanut allergy resolve by 6 years old,” Kayla M. Parker, BSc, PhD candidate at Murdoch Children's Research Institute and Department of Pediatrics, University of Melbourne, told Healio.
The study followed 156 infants in Melbourne, Australia, with confirmed peanut allergies and administered questionnaires at age 4, 6, and 10 years along with skin prick tests, blood tests, and oral food challenges.
“Little was known about the natural progression of peanut allergy and which children with peanut allergy are more likely to outgrow it,” Parker said. “We investigated the natural history of peanut allergy from infancy to childhood and changes in peanut allergy-specific antibodies using the HealthNuts study. We further explored if these peanut antibodies in the blood could be used as biomarkers to identify naturally resolving or persistent peanut allergy from infancy through to primary school years.”
The HealthNuts study ran from August 2007 to September 2011 across Melbourne and recruited 5,276 infants aged 11 to 15 months. The infants underwent SPTs for peanuts, sesame, egg and either shellfish or milk. Those with SPT wheal sizes of at least 1 mm to peanut, sesame or egg were then invited to the Royal Children's Hospital, Melbourne, for further testing.
When the infants turned age 4 years, those who took an OFC or reported new food reactions that could indicate an IgE-mediated allergy were further assessed with an SPT to peanuts, sesame, egg, milk, wheat, almond, cashew and hazelnut. Blood also was collected. The same protocol was followed at ages 6 and 10 years.
Biomarkers measured in this study included total IgE, peanut specific IgE (sIgE), peanut sIgE/total IgE (tIgE) ratio, peanut specific IgG4 (sIgG4), peanut sIgG4/sIgE ratio, Ara h 2 sIgE, Ara h 2 sIgE/tIgE ratio, Ara h 2 sIgG4 and Ara h 2 sIgG4/sIgE ratio.
At 10 years, 91% (n = 142; mean age, 10.4 years) of the 156 children with a challenge-confirmed peanut allergy at age 12 months participated in the follow-up, with 70.5% (n = 110) completing an allergy assessment, 20.5% (n = 32) only completing a questionnaire. Peanut allergy outcomes were determined for 97.9% (n = 139).
For the biomarker analysis, 134 children who completed a blood sample at age 1 year and who had either a persistent peanut allergy at age 10 years (n = 95) or a resolved peanut allergy by age 10 years (n = 39) were included in the analytic sample.
A peanut allergy was resolved in 33.9% (95% CI, 25.3%-43.3%; n = 39) and remained in 66.1% (95% CI, 56.7%-74.7%; n = 76) of 115 children. Researchers showed that 38 of the 39 children that outgrew their peanut allergy did so by age 6 years.
The researchers noted that children who remained allergic to peanuts were more likely to have a parent born in East Asia or eczema, as well as a lower cumulative reaction dose on peanut OFC or sensitization to tree nuts based on SPT at age 1 year.
Between children with a persistent vs. resolved peanut allergy phenotype, researchers found that differences in median biomarker levels at age 1 year included peanut SPT (P = .004), peanut sIgE (P = .02) and peanut sIgG4 (P = .09).
The probability of a peanut allergy persisting at age 10 years was greater with an increase in age 1 year peanut sIgE (OR = 1.96; 95% CI = 1.16-3.29 per interquartile ratio [IQR] increase), sIgE/tIgE ratio (OR = 7.88; 95% CI = 2.47-25.2 per IQR increase) and SPT (OR = 2.02; 95% CI = 1.23-3.3 per IQR increase).
“We found unique changes over time in the peanut-specific antibody biomarkers, IgE and IgG4 between children that remained peanut allergic compared to the children with a resolved peanut allergy,” Parker said.
“Children with a persistent peanut allergy had increasing peanut IgE over time,” she continued. “They also had an initial spike in peanut IgG4 between ages 1 and 4 before it plateaued until 10 years old. Whereas in children that had a resolved peanut allergy, their peanut IgE decreased after infancy and their peanut IgG4 levels continued to increase until 10 years old.”
Parker stated that even though peanut allergies are often considered to be lifelong and previous studies suggest that only 20% of children will outgrow them, her study findings showed that more children are outgrowing their peanut allergy than previously thought.
“Although infants with a persistent peanut allergy were more likely to have higher peanut IgE levels, eczema or multiple allergies, there was no concrete factor at infancy that could predict their outcome,” she said. “Instead, we found it was the changes over time in their peanut-specific antibody biomarkers that revealed who was more likely to outgrow their peanut allergy.”
Parker further explained that she hopes her team’s findings will help allergists in the clinical management of food allergy when counselling families with a new diagnosis or when deciding how often to review their patients.
“The HealthNuts study is continuing to follow up these children into adolescence to understand the natural history of food allergy and long-term impacts of other health outcomes,” she said.
Perspective
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Peanut allergy is a serious and life-threatening condition, and understanding biomarkers associated with persistent peanut allergy or resolving peanut allergy could have significant implications for clinical practice.
In this study, 33.9% of infants with challenge-confirmed peanut allergy at age 1 year outgrew their peanut allergy by age 10 years, which is consistent with what I have seen in clinical practice, where roughly 20% to 30% of patients outgrow peanut allergy over time.
One finding I found particularly interesting is that in children with early onset peanut allergy, the development of peanut tolerance occurs mostly by age 6 years and changes in peanut allergy status after that point are uncommon.
In all of my peanut-allergic patients, I always obtain SPT as well as peanut sIgE testing to establish a baseline. I also monitor these test results over time.
For peanut allergy specifically, I have seen that improvements in peanut sIgE and Ara h 2 sIgE can potentially be a sign of resolving peanut allergy. I have treated many of my peanut-allergic patients with oral immunotherapy desensitization that is known to decrease peanut sIgE and increase peanut sIgG4.
It is always important to obtain both SPT and sIgE testing to establish a baseline in food allergic patients during the initial visit, as well as with each follow-up visit to monitor the trends of test results over time.
Longitudinal monitoring of peanut sIgE and Ara h 2 sIgE component testing in particular can help predict potential outcomes and guide management strategies for peanut allergy in children.
Specific IgE testing and ratios could potentially serve as biomarkers for predicting outcomes in peanut allergy. Decreasing peanut and Ara h 2 sIgE, as well as increasing IgG4 and IgG4/sIgE can be associated with peanut allergy resolution. Regular monitoring of peanut and Ara h 2 sIgE and IgG4 levels over time may provide valuable insights into the natural resolution or improvement of peanut allergy in children.
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Parker KM, et al. Allergy. 2024;doi:10.1111/all.16111.
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