Diverse Food Allergen IgG Reactivities Are Associated With Food Allergies in the Boston Birth Cohort

ABSTRACT Background Food allergies in children represent a growing clinical and public health concern worldwide, yet their causes remain poorly understood. Objective To investigate the role of circulating IgG antibodies to food allergens and viral antigens at birth and during early childhood in the development of food allergies, using data from a prospective birth cohort. Methods This study included 458 children composed of 80 with food allergies, 151 with food sensitization, and 227 who were non‐allergic and non‐sensitized to these food allergens and had no other allergic diseases (asthma, atopic dermatitis, and allergic rhinitis). Phage ImmunoPrecipitation Sequencing (PhIP‐Seq) was used to profile the IgG antibody reactome against thousands of environmental antigens (including allergens and viruses) in matched cord blood and childhood plasma samples from these children. We then investigated whether IgG profiles were associated with allergies to egg, milk, and peanut. Results Children with food allergies had a significantly elevated diversity of IgG reactivity to thousands of allergen peptides in early childhood compared to non‐allergic controls. No such associations were found in cord blood at birth. We identified that peanut‐allergic children have higher IgG reactivity to 24 peanut peptides, and egg‐allergic children had higher IgG reactivity to 17 egg peptides compared to non‐allergic controls. Additionally, patterns of shared IgG reactivity to wheat peptides were observed across different food allergy groups in early childhood. Notably, milk‐allergic children exhibited lower magnitudes of IgG reactivities to eight milk peptides in cord blood and reduced IgG reactivities to enteroviral peptides during childhood (all FDR < 0.05), relative to non‐allergic controls. Conclusion These results suggest that unbiased IgG reactome profiling in a prospective birth cohort provides new insights into early life immune regulation and its influence on childhood allergic phenotypes.