Dataset Information

Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy.

ABSTRACT: Food allergy poses a significant clinical and public health burden affecting 2-10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) underpins this suboptimal response. Infants who fail to resolve food allergy in later childhood exhibit cumulative increases in epigenetic disruption at T cell activation genes and poorer lymphoproliferative responses compared to children who resolved food allergy. Our data indicate epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex, and likely reflects pathways modified by gene-environment interactions in food allergy.

SUBMITTER: Martino D

PROVIDER: S-EPMC6098117 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy.

Martino David D Neeland Melanie M Dang Thanh T Cobb Joanna J Ellis Justine J Barnett Alice A Tang Mimi M Vuillermin Peter P Allen Katrina K Saffery Richard R

Nature communications 20180817 1

Food allergy poses a significant clinical and public health burden affecting 2-10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic ...[more]

PMID: 30120223

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Project description:Background:The role of infant feeding for food allergy in children is unclear and studies have not addressed simultaneous exposures to different foods. The goal of this study was to analyze existing data on feeding practices that represent realistic exposure and assess the risk of food allergy symptoms and food allergy in children. Methods:The Infant Feeding Practices Study II conducted by the CDC and US-FDA enrolled pregnant women and collected infant feeding information using nine repeated surveys. Participants were re-contacted after 6 years. Food allergy data were collected at 4, 9, 12, and 72?months. In total, 1387 participants had complete infant feeding pattern data for 6 months and information on food allergy symptoms and doctors' diagnosed food allergy. Feeding patterns constituted six groups: 3-months of feeding at breast followed by mixed feeding, 3-months of breast milk and bottled milk followed by mixed feeding, 1-month of feeding at breast followed by mixed feeding, 6-months of mixed feeding i.e., concurrent feeding of breast milk, bottled milk and formula, 2-3?months of formula followed by formula and solid food, and formula and solid food since the first month. To estimate risks of food allergy, we used linear mixed models, controlling for potential confounders. Results:Of the 328 children with food allergy symptoms in infancy and at 6 years, 52 had persistent symptoms from infancy. Children exposed to mixed feeding had a higher risk of food allergy symptoms (Risk Ratio [RR] 1.54; 95% Confidence Interval [CI] 1.04, 2.29) compared to 3-months of feeding at breast adjusted for confounding. No statistically significant risk of infant feeding patterns was found for doctors' diagnosed food allergy. Paternal allergy posed a higher risk for food allergy symptoms (RR 1.36; 95% CI 1.01, 1.83). Prenatal maternal smoking increased the risk for doctors' diagnosed food allergy (RR 2.97; 95% CI 1.53, 5.79). Conclusions:Analysis of this prospective birth cohort suggest that introduction of multiple feeding source may lead to food allergy symptoms. Future efforts are needed to determine acceptable approaches to improve the ascertainment of food allergy in children and the role of infant feeding.

Dataset Information

Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy.

Publications

Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy.

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