Placental Epigenetic Alterations and IL-10 Dysregulation Drive Early Persistent Food Allergy

The mechanisms underlying distinct food allergy (FA) trajectories in children remain unclear. This study aimed to classify FA trajectories and examine differences in placental DNA methylation and serum cytokine profiles.

A total of 1518 children from the COCOA (COhort for Childhood Origin of Asthma and Allergic Diseases) study, followed until age 7, were classified into FA trajectories using group-based trajectory modeling. Serum cytokine levels were measured at ages 3 and 7 years. Placental methylation profiling was performed with Infinium MethylationEPIC BeadChip.

Children were classified into four trajectories: no FA (87.3%), early remission (6.9%), early persistent (4.6%), and late remission (1.1%). At ages 3 and 7, the early persistent FA trajectory exhibited higher interleukin (IL)-4, IL-5, and IL-6 levels than the no FA trajectory. At age 3, IL-10 levels were lower in the early persistent trajectory than in the late remission trajectory. In DNA methylation analysis, the Ribosomal Protein S6 Kinase A2 (RPS6KA2) and Germinal Center Associated Signaling And Motility Like (GCSAML) genes were significantly hypermethylated in the early persistent FA trajectory compared to the no FA and early remission trajectory (p < 0.05). GCSAML methylation was positively correlated with total IgE, egg white-specific IgE, early-life eosinophils, and IL-5 at age 7 (all p < 0.05).

Hypermethylation of RPS6KA2 and GCSAML, reduced IL-10 levels, and elevated Th2 cytokines were associated with early persistent FA trajectory, potentially influencing its allergic inflammation and persistence.