Do non-allergic people produce antibodies against food proteins?

Yes. In a population-scale study of 1,003 Israeli adults, Leviatan and colleagues showed that many common food antigens elicited systemic IgG antibodies in up to 50% of non-allergic individuals. These IgG responses are widespread, asymptomatic, and distinct from the IgE-driven antibody responses that cause classical food allergies.

What antibody class dominates the response to dietary proteins?

IgG. Parallel PhIP-Seq experiments using protein A versus protein G beads (Pearson R=0.90) and IgG-specific versus IgA-specific capture antibodies confirmed that the systemic antibody binding signal against food peptides is overwhelmingly IgG, not IgA or IgE, in the studied non-allergic cohort.

How stable are food-directed IgG antibody responses over time?

In a 214-individual longitudinal subcohort with samples collected approximately five years apart, food-directed IgG epitope repertoires were strongly correlated within individuals but not between random pairs. Stability was comparable to or exceeded the discriminatory power of antibody profiles against pathogens, suggesting these repertoires function as durable molecular fingerprints.

Does diet shape the IgG antibody repertoire?

Yes. The authors found that recorded dietary intake of specific food proteins correlated with corresponding IgG binding profiles, supporting a causal link between consumption and seroreactivity. Machine-learning models trained on antibody repertoires also predicted age (R-squared = 0.31) and gender, with SHAP analysis attributing predictive weight to peptides from milk, rice, certain legumes, herpesviruses, Streptococcus species, and dust mite antigens.

Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals

1,003 adults profiled across 58,233 phage-displayed allergen peptides reveal a five-year-stable IgG fingerprint of dietary history.

Leviatan S, Vogl T, Klompus S, Kalka IN, Weinberger A, Segal E.

Immunity · December 13, 2022 · DOI: 10.1016/j.immuni.2022.11.004

How to cite

AMA

Leviatan S, Vogl T, Klompus S, Kalka IN, Weinberger A, Segal E. Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals. Immunity. 2022;55(12):2454-2469.e6. doi:10.1016/j.immuni.2022.11.004

APA

Leviatan, S., Vogl, T., Klompus, S., Kalka, I. N., Weinberger, A., & Segal, E. (2022). Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals. Immunity, 55(12), 2454–2469.e6. https://doi.org/10.1016/j.immuni.2022.11.004

BibTeX

@article{leviatan2022allergenic,
  title   = {Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals},
  author  = {Leviatan, Sigal and Vogl, Thomas and Klompus, Shelley and Kalka, Iris N. and Weinberger, Adina and Segal, Eran},
  journal = {Immunity},
  volume  = {55},
  number  = {12},
  pages   = {2454--2469.e6},
  year    = {2022},
  doi     = {10.1016/j.immuni.2022.11.004}
}

Leviatan and colleagues used PhIP-Seq to measure systemic IgG binding against tens of thousands of food and environmental allergen peptides in a population-scale Israeli cohort. They found that common food antigens elicit measurable systemic IgG in up to half of non-allergic adults — far above clinical allergy prevalence — and that those antibody repertoires correlate with dietary intake. In a five-year longitudinal subcohort, the IgG epitope pattern was highly correlated within individuals but not between random pairs, behaving as a durable molecular fingerprint of an individual's diet.

Read publication at Immunity

In this publication:

1,003 Israeli adults profiled across 58,233 phage-displayed allergen peptides via PhIP-Seq, totaling 58 million antibody–peptide interactions.
Common food antigens elicited systemic IgG in up to 50% of non-allergic adults — far above the <1% population prevalence of food allergy.
An average of 322 ± 106 peptides were significantly enriched per person; hierarchical clustering surfaced 13 antibody-binding clusters spanning food and environmental antigens.
In a 214-person longitudinal subcohort sampled five years apart, IgG epitope repertoires were highly correlated within individuals but not between random pairs — a durable serological fingerprint of dietary history.

This study repositions food-directed IgG from a presumed pathology signal to a quiet, baseline immunological record of consumption. Using PhIP-Seq (phage immunoprecipitation sequencing), the authors profiled IgG binding against 58,233 peptides drawn from food and environmental allergen databases in 1,003 Israeli adults — 58 million antibody–peptide interactions in total — and detected, on average, 322 ± 106 peptides significantly enriched per person.

Hierarchical clustering surfaced 13 antibody-binding clusters spanning food and environmental antigens, with extensive cross-reactivity across phylogenetically related cereals, milk proteins, poultry, and legumes. Parallel IgG- and IgA-specific capture experiments confirmed the binding signal is overwhelmingly IgG. In a 214-individual longitudinal subcohort sampled five years apart, food-directed IgG epitope repertoires were highly correlated within individuals but not between random pairs — functioning as a five-year-stable molecular fingerprint of dietary history.

For allergists separating clinically meaningful IgE-mediated sensitization from background reactivity, the work quantifies the non-allergic IgG baseline that any food-allergy biomarker must be measured against. For nutrition and microbiome researchers, it offers a serological lens on the diet–immune axis that can be triangulated with diet diaries, anthropometrics, and microbiome composition in the same cohort.

Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals

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