IgG Reactivity Patterns in Pediatric Food Allergy, With Julia Angkeow

New findings suggest that immunoglobulin G (IgG) responses may provide mechanistic insight into pediatric food allergy, with children with peanut and egg allergies showing increased IgG reactivity to food allergen peptides in early childhood.

The analysis, conducted using Phage ImmunoPrecipitation Sequencing (PhIP-Seq), included 458 children from the Boston Birth Cohort. Among them were 80 children with food allergies, 151 with sensitization, and 227 non-allergic controls. Investigators profiled IgG responses to thousands of peptide epitopes at birth and in early childhood.

Compared to controls, peanut-allergic children had greater IgG reactivity to 24 peanut peptides, and egg-allergic children had greater IgG reactivity to 17 egg peptides. These differences were not observed in cord blood, suggesting that postnatal immune development plays a central role.

The study showed modest correlations between IgE and IgG measurements for peanut (P =.034) in peanut-allergic children, for egg (P =.24) in egg-allergic children, and for wheat (P < 0.01) in children with any food allergy.

“These modest correlations suggest that IGE and IgG are partially related, but they're distinct parts of the immune response,” Julia W. Angkeow, a PhD candidate at the Washington University School of Medicine in St. Louis and former research technologist at Johns Hopkins Medicine, told HCPLive. “PhIP-Seq captures all IgG subclasses, which reflects…a broader antigen exposure and immune memory.”

Milk allergy presented a distinct pattern. Lower IgG reactivity to 8 milk peptides was observed in cord blood among children who later developed milk allergy, alongside reduced IgG responses to enteroviral peptides in childhood (all FDR <0.05). These findings may reflect altered early immune priming and are consistent with aspects of the hygiene hypothesis, although causality has not been established.

Angkeow cautioned that IgG profiling, particularly via PhIP-Seq, is not intended for clinical diagnosis of food allergy. Instead, the technology provides a high-throughput, low-cost method for mapping epitope-level immune responses across thousands of antigens simultaneously, thereby far exceeding the scope of conventional ELISA assays. Epitope-level IgG profiling may help differentiate tolerance from sensitization and inform early risk stratification, but longitudinal studies beginning in pregnancy and extending through early childhood will be needed to determine whether these IgG patterns are predictive markers or downstream consequences of allergic disease.

“I think that IgG reactant profiling could eventually inform early risk stratification or prevention strategies if the patterns that we're seeing or specific patterns in general are consistently replicated, and if they always come before allergy development across multiple different cohorts,” Angkeow said, “But we're not there yet, and there needs to be a lot of replication and mechanistic validation and protective studies before we can translate this into prevention strategies.”

Angkeow has no relevant disclosures.

References

1. Angkeow JW, Hong X, Thakar M, et al. Diverse food allergen IgG reactivities are associated with food allergies in the Boston Birth Cohort. Allergy. 2026. doi:10.1111/all.70246. https://pubmed.ncbi.nlm.nih.gov/41689198/

2. Angkeow J. Early-Life IgG Patterns Linked to Childhood Food Allergy, With Julia Angkeow. HCPLive. Published February 24, 2026. Accessed on March 24, 2026. https://www.hcplive.com/view/early-life-igg-patterns-linked-childhood-food-allergy-julia-angkeow