Julia W. Angkeow, a PhD candidate and former research technologist at Johns Hopkins Medicine

Julia Angkeow

IgG Reactivity Patterns in Pediatric Food Allergy, With Julia Angkeow

New findings suggest that immunoglobulin G (IgG) responses may provide mechanistic insight into pediatric

 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 (

 =.034) in peanut-allergic children, for egg (

 =.24) in egg-allergic children, and for wheat (

 < 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 

 “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 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/

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

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Angkeow discusses a recent study finding that PhIP-Seq analysis links diverse IgG responses to food allergy phenotypes.

Early-Life IgG Patterns Linked to Childhood Food Allergy, With Julia Angkeow

 in early childhood, but not observed at birth.

, investigator Julia W. Angkeow, a PhD candidate and former research technologist at Johns Hopkins Medicine, emphasized that the study was intended not to validate IgG as a diagnostic tool, but to map the broader IgG reactome in an unbiased way.

Using Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a high-throughput antibody profiling platform developed in their laboratory, Angkeow and colleagues analyzed IgG responses to hundreds of thousands of peptides derived from allergens, viruses, toxins, and human proteins.

“It gives us a broad picture of what someone has been exposed to in their environment and how their immune system has responded to their past and ongoing immune exposures,” Angkeow told 

. “What we found through this study is that we can use PhIP-Seq to identify IgG patterns that are distinct between allergic and allergic children, and they're also distinct in early childhood versus at birth.”

The prospective cohort included 458 children: 80 with food allergy, 151 with food sensitization, and 227 non-allergic controls without other atopic disease.1 Investigators profiled matched cord blood and early-childhood plasma samples. In early childhood, but not in cord blood, children with food allergy exhibited significantly greater diversity of IgG reactivity to allergen peptides (false discovery rate < 0.05).

Peanut-allergic children demonstrated greater IgG reactivity to 24 peanut peptides, while egg-allergic children showed increased responses to 17 egg peptides. Angkeow cautioned clinicians against overinterpreting these findings. She noted that elevated IgG likely reflects ongoing or repeated immune exposure and should not be interpreted as protective, pathogenic, or diagnostic. Professional societies have previously advised against IgG-based food sensitivity testing due to lack of clinical validity.2

One unexpected finding was lower cord blood IgG reactivity to milk peptides among children who later developed milk allergy. While this observation is consistent with the hypothesis that maternally transferred allergen-specific IgG could be protective, Angkeow emphasized that the study measured total IgG and did not distinguish subclasses with differing immunologic functions.

“There needs to be more mechanistic studies, such as profiling different IgG subclasses to test that directly,” she said.

Angkeow JW, Hong X, Thakar M, et al. Diverse food allergen IgG reactivities are associated with food allergies in the Boston Birth Cohort. 

McGill University. Office for Science and Society. Published August 30, 2024. Accessed February 24, 2026. 

https://www.mcgill.ca/oss/article/medical-critical-thinking-health-and-nutrition/no-tolerance-igg-food-intolerance-tests

PhIP-Seq analysis in the Boston Birth Cohort found distinct early-childhood IgG patterns in food allergy, but investigators caution against diagnostic use of IgG testing.

Julia Angkeow

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