Paediatrics (RCH) - Research Publications
Permanent URI for this collection
Search Results
1 - 7 of 7
-
ItemSpecific oral tolerance induction in childhood(WILEY, 2016-12)Food allergy continues to be a significant public health concern for which there are no approved treatments and management strategies primarily include allergen avoidance and pharmacological measures for accidental exposures. Food allergy is thought to result from either a failure to establish oral tolerance or the breakdown of existing oral tolerance, and therefore, experimental preventative and treatment strategies are now aimed at inducing specific oral tolerance. This may occur in infancy prior to the development of food allergy through the optimal timing of dietary exposure (primary oral tolerance induction) or as a treatment for established food allergy through oral immunotherapy (secondary oral tolerance induction). Trials examining the effectiveness of early dietary allergen exposure to prevent food allergy have yielded promising results for peanut allergy but not so for other allergens, although the results of several trials are yet to be published. Although infant feeding guidelines no longer advise to avoid allergenic foods and exposure to food allergens orally is an important step in inducing food tolerance by the immune system, evidence regarding the optimal timing, dose and form of these foods into the infant's diet is lacking. Likewise, oral immunotherapy trials appear promising for inducing desensitization; however, the long-term efficacy in achieving sustained desensitization and optimal protocols to achieve this is unknown. More research is needed in this emerging field.
-
ItemB-cell phenotype and function in infants with egg allergy(WILEY, 2019-05)
-
ItemEgg allergen specific IgE diversity predicts resolution of egg allergy in the population cohort HealthNuts(WILEY, 2019-02)BACKGROUND: IgE-mediated egg allergy presents as one of the most common food allergies in children. Measurement of egg white specific IgE (sIgE) levels in serum or skin prick test has been shown to be a poor predictor of clinical allergy to raw egg white, and also to baked or cooked egg. Recent developments in component resolved diagnostic (CRD) technology have enabled us to improve the way in which we diagnose and predict peanut allergy by examining IgE specificity to individual peptides. OBJECTIVES: We aimed to investigate whether egg CRD could improve current methods to diagnose various egg allergy phenotypes as well as predict the development of tolerance to egg. METHODS: Using the HealthNuts cohort of food challenge-proven egg allergic and egg-sensitized and egg-tolerant, age-matched 12-month infants with longitudinal follow-up at 2 and 4 years (n = 451), we measured serum egg white, Gal d 1, 2, 3 and 5 sIgE using ImmunoCAP. RESULTS: Gal d 1 sensitization increased the risk of persistent egg allergy by 2.5-fold. The production of sIgE to all four egg allergens (Gal d 1, 2, 3 or 5) increased the risk of having persistent raw egg allergy fourfold (OR 4.19 (95% CI: 1.25-14.07). We did not find any improvements of using Gal d 1, 2, 3 or 5 to diagnose current egg allergy compared to egg white sIgE. CONCLUSION: Sensitization to multiple egg allergens Gal d 1, 2, 3 or 5 may be a prognostic marker that could be useful for patient management and identifying individuals at risk of developing persistent egg allergy.
-
ItemEpigenetic dysregulation of naive CD4+T-cell activation genes in childhood food allergy(NATURE PORTFOLIO, 2018-08-17)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.
-
ItemThe Impact of Family History of Allergy on Risk of Food Allergy: A Population-Based Study of Infants(MDPI AG, 2013-11)The apparent rapid increase in IgE-mediated food allergy and its implications are now widely recognized, but little is known about the relationship between family history (an indirect measure of genetic risk) and the risk of food allergy. In a population-based study of 5,276 one year old infants (HealthNuts), the prevalence of oral food challenge-confirmed food allergy was measured. Associations between family history of allergic disease and food allergy in infants were examined using multiple logistic regression. Food allergy was diagnosed in 534 infants. Compared to those with no family history of allergic disease, children meeting the current definition of "high risk" for allergic disease (one immediate family member with a history of any allergic disease) showed only a modest increase (OR 1.4, 95% CI 1.1-1.7) in food allergy, while having two or more allergic family members was more strongly predictive of food allergy in the child (OR 1.8, 95% CI 1.5-2.3). There were also differences in the associations between family history and egg and peanut allergy in the child. Re-defining "high risk" as two or more allergic family members may be more useful for identification of groups with a significantly increased risk of food allergy both clinically and within research studies.
-
ItemDebates in allergy medicine: baked egg and milk do not accelerate tolerance to egg and milk(ELSEVIER, 2016-01-26)There is emerging evidence that children with egg and cow's milk allergy who can tolerate these allergens cooked in baked goods are more likely to develop tolerance. As a result a hypothesis has arisen that exposure to egg and milk in baked goods may hasten tolerance development; however, it is unclear whether children who develop tolerance do so because they have ingested low levels of egg or milk in baked products. An alternative explanation for the improved prognosis in those who can tolerate food allergens in the baked form is that tolerance to egg and milk in baked goods is simply an indicator of a phenotype that is less likely to be persistent. We discuss the role that the baked egg or milk allergy phenotype plays on predicting tolerance development and suggest that it is the phenotype of the disease rather than exposure to altered allergens that is the strongest predictor of tolerance development.
-
Item