J R Metcalfe1, N D'Vaz1,2, M Makrides3,4,5, M S Gold5,6, P Quinn6, C E West1,7, R Loh8, S L Prescott1,2,8, D J Palmer1,3. 1. School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia. 2. Telethon KIDS Institute, The University of Western Australia, Perth, WA, Australia. 3. Women's & Children's Health Research Institute, Adelaide, SA, Australia. 4. Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, SA, Australia. 5. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia. 6. Children, Youth and Women's Health Service, Adelaide, SA, Australia. 7. Department of Clinical Sciences, Pediatrics, Umeå University, Umea, Sweden. 8. Department of Immunology, Princess Margaret Hospital, Perth, WA, Australia.
Abstract
BACKGROUND: Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure. OBJECTIVE: To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy. METHODS:Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive 'early egg' or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge. RESULTS: In 4-month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by 'early' introduction of egg. CONCLUSIONS & CLINICAL RELEVANCE: Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.
RCT Entities:
BACKGROUND: Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure. OBJECTIVE: To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy. METHODS: Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive 'early egg' or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge. RESULTS: In 4-month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by 'early' introduction of egg. CONCLUSIONS & CLINICAL RELEVANCE: Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.
Authors: Debra J Palmer; Thomas R Sullivan; Dianne E Campbell; Ralph Nanan; Michael S Gold; Peter S Hsu; Merryn J Netting; Vicki McWilliam; Jennifer J Koplin; Kirsten P Perrett; Patrick Quinn; Michael O'Sullivan; Susan L Prescott; Rosalie Grivell; Maria Makrides Journal: BMJ Open Date: 2022-06-13 Impact factor: 3.006
Authors: Michael G Sherenian; Arjun Kothari; Jocelyn M Biagini; John W Kroner; Asel Baatyrbek Kyzy; Elisabet Johannson; Gowtham Atluri; Hua He; Lisa J Martin; Gurjit K Khurana Hershey Journal: Clin Exp Allergy Date: 2021-03-21 Impact factor: 5.401