Longitudinal egg-specific regulatory T- and B-cell development: Insights from primary prevention clinical trials examining the timing of egg introduction.

Catherine L Lai, Dianne E Campbell, Debra J Palmer, Maria Makrides, Brigitte Santner-Nanan, Michael Gold, John Wei-Liang Tan, Carol Valerio, Ralph Nanan, Susan L Prescott, Peter S Hsu

Journal: Allergy 2021;76(5):1385-1397

PMID: 33040362

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Abstract

BACKGROUND

Egg allergy affects almost 1 in 10 Australian infants. Early egg introduction has been associated with a reduced risk in developing egg allergy; however, the immune mechanisms underlying this protection remain unclear.

OBJECTIVE

To examine the role of regulatory immune cells in tolerance induction during early egg introduction.

METHODS

Cryopreserved peripheral blood mononuclear cells (PBMC) were obtained from infants from 2 randomized controlled trials of early introduction of egg for the primary prevention of egg allergy; BEAT (at 12 months, n = 42) and STEP (at 5 months n = 82; 12 months n = 82) study cohorts. In vitro ovalbumin-stimulated PBMC were analyzed by flow cytometry for presence of ovalbumin-specific regulatory T cells, using activation markers, FoxP3, and IL-10 expression. Ovalbumin-specific regulatory B cells were identified by co-expression of fluorescence-conjugated ovalbumin and IL-10.

RESULTS

Specific, age-dependent expansion of ovalbumin-specific regulatory T cells was only observed in infants who (a) had early egg introduction and (b) did not have egg allergy at 12 months. This expansion was blunted or impaired in children who did not undergo early egg introduction and in those with clinical egg allergy at 12 months. Infants with egg allergy at 12 months of age also had reduced frequency of ovalbumin-specific regulatory B cells compared to egg-tolerant infants.

CONCLUSION

Early egg introduction and clinical tolerance to egg were associated with expansion of ovalbumin-specific T and B regulatory cells, which may be an important developmental process for tolerance acquisition to food allergens.

Address: Department of Allergy and Immunology, The Children's Hospital at Westmead, Westmead, NSW, Australia.; Kids Research Institute, The Children's Hospital at Westmead, Westmead, NSW, Australia.; Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, NSW, Australia.; Murdoch Children's Research Institute, Centre for Food Allergy Research (CFAR), Parkville, Vic, Australia.; Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia.; School of Medicine, The University of Western Australia, Crawley, WA, Australia.; South Australian Health and Medical Research Institute, SAHMRI Women and Kids, Adelaide, SA, Australia.; School of Medicine, University of Adelaide, Adelaide, SA, Australia.; Sydney Medical School Nepean and Charles Perkins Centre Nepean, The University of Sydney, Kingswood, NSW, Australia.; Discipline of Paediatrics, School of Medicine, University of Adelaide, Adelaide, SA, Australia.; The ORIGINS Project, Telethon Kids Institute, University of Western Australia, Perth Children's Hospital, Nedlands, WA, Australia.; InVIVO Planetary Health of the Worldwide Universities Network (WUN), West New York, NJ, USA.

DOI: 10.1111/all.14621

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MeSH Terms: Allergens, Australia, B-Lymphocytes, Child, Egg Hypersensitivity, Humans, Infant, Leukocytes, Mononuclear, Ovalbumin, Primary Prevention