Project Details

Early life immune biomarkers of persistent childhood food allergy

Melanie Neeland, PhD

Summary

BACKGROUND: The rates of food allergies and food-induced anaphylaxis in Australia have increased five-fold in the last 15-20 years, particularly in children under the age of five. Using gold standard oral food challenge outcomes, we have recently shown that, of 12-month-old Australian infants, 9% were allergic to egg and 3% were allergic to peanuts. GAP: A proportion of food allergic infants naturally outgrow their food allergy in childhood, with immunological tolerance developing in 47% of egg allergic children by 2 years of age and 22% of peanut allergic children by 4 years of age. The immunological mechanisms responsible for the development of food allergy in infancy and the induction of natural tolerance in childhood are poorly understood. Our preliminary data shows that infants with a hyper-responsive innate immune profile in the first year of life are prone to develop persistent food allergy, however, further mechanistic evidence is required to determine if these findings can be used as a biomarker to predict disease outcomes in childhood. HYPOTHESIS: We hypothesize that innate immune hyper-responsiveness in the first year of life is responsible for the persistence of allergic immune responses to foods in childhood. Specifically, we hypothesize that hyper-responsive innate cells in the first year of life are responsible for skewing naïve CD4 T cells toward an allergic Th2 phenotype, resulting in greater levels of specific IgE that leads to the persistence of food allergy in childhood. METHODS: This research project will use cryopreserved peripheral blood mononuclear cells (PBMCs) collected from food allergic and control 12-month-old infants in the Australian HealthNuts study. Food allergic infants will have either persistent or transient food allergy outcomes in childhood. The functional innate immune response associated with persistent and transient phenotypes of pediatric food allergy will be comprehensively analyzed. RESULTS: We show that purified blood monocytes from infants with food allergy produce more of the granulocyte recruiting factors CCL2, CCL3 and CCL5 following in vitro endotoxin exposure relative to non-allergic infants. We also show that food allergic infants have higher monocyte:CD4 T cell ratios than non-allergic infants, and that activated monocytes from food allergic children can skew naïve CD4 T cells towards a Th2 phenotype. Additionally, both allergen and bacterial stimulation increased B cell-derived IL-8 production from infants with persistent food allergic outcomes relative to infants with transient allergy. IMPACT: This project provides a unique opportunity to discover novel biomarkers that are useful in identifying active and persistent allergy, and predicting allergy resolution. The ability to understand and predict food allergy outcomes in early life will have important implications for current patient care, identifying high risk infants whose food allergy is likely to persist into childhood.

Publications:

Neeland, Melanie R., David J. Martino, Thanh D. Dang, Jennifer J. Koplin, Rachel L. Peters, Alexander Grishin, Shyamali C. Dharmage et al. "B-cell phenotype and function in infants with egg allergy." Allergy 74, no. 5 (2019): 1022.

Neeland, Melanie R., Jennifer J. Koplin, Thanh D. Dang, Shyamali C. Dharmage, Mimi L. Tang, Susan L. Prescott, Richard Saffery, David J. Martino, and Katrina J. Allen. "Early life innate immune signatures of persistent food allergy." Journal of Allergy and Clinical Immunology 142, no. 3 (2018): 857-864.