Children with nut allergies have impaired gene expression of Toll‐like receptors pathway

Poole, Ashlyn; Song, Yong; O’Sullivan, Michael; Lee, Khui Hung; Metcalfe, Jessica; Guo, Jing; Brown, Helen; Mullins, Ben; Loh, Richard; Zhang, Guicheng

doi:10.1111/pai.13246

Cited by 9 publications

(8 citation statements)

References 34 publications

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“…DNA methylation was assessed using a restriction enzyme digestion approach (EpiTect Methyl II qPCR System after digestion with methylation‐sensitive restriction enzymes). There was no statistically significant difference in TLR2 and CD14 promoter methylation between groups 27 …”

Section: Resultsmentioning

confidence: 73%

“…The search strategy generated 366 citations, of which 350 were excluded, leaving 16 studies [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] eligible for the systematic review (Figure 1 and Tables S1, S2), which were mainly focused on FA in children. Among them, seven assessed the epigenetic predictors of FA using a candidate gene approach and focused on the Th1-Th2 imbalance, [22][23][24]31 the alteration of regulatory T cell function, 23,25,26 the TLR2 pathway 27 and the alteration of digestive barrier integrity 28 (Table 1). Nine studies evaluated the epigenetic predictors of FA using an epigenome-wide association study design and focused on peanut allergy, [29][30][31] cow's milk allergy 32,33 or various food allergens [34][35][36][37] (Tables 2 and 3).…”

Section: Literature Search Resultsmentioning

confidence: 99%

“…The expression of FOXP3 is regulated by DNA methylation in a highly conserved sequence within the Treg cell‐specific demethylation region (TSDR) 40 . In the contrary, TLR2 was found as a potential gene with epivariation implicated in FA in the targeted study by Poole et al 27 TLR2 is a master component of innate immunity. It is highly expressed in innate immune cells, such as macrophages and dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

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Epigenome alterations in food allergy: A systematic review of candidate gene and epigenome‐wide association studies

Safar

Oussalah

Mayorga

et al. 2023

Clin Experimental Allergy

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Objective:The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA).Design: A systematic review of the literature and meta-analysis were carried out within several databases. However, the risk of bias in the included articles was not evaluated.Data sources: PubMed, Cochrane Database of Systematic Reviews, and Web of Science were used to search up to July 2022. Eligibility criteria:We included targeted and epigenome-wide association studies (EWASs) that assessed DNA methylome alterations in association with FA in adult or paediatric populations.Results: Among 366 publications, only 16 were retained, which were mainly focused on FA in children. Seven candidate gene-targeted studies found associations in Th1/ Th2 imbalance (IL4, IL5, IL10, INFG, IL2 and IL12B genes), regulatory T cell function (FOXP3 gene), Toll-like receptors pathway (TLR2, CD14 genes) and digestive barrier integrity (FLG gene). Nine EWAS assessed the association with peanut allergy (n = 3), cow's milk allergy (n = 2) or various food allergens (n = 4). They highlighted 11 differentially methylated loci in at least two studies (RPS6KA2, CAMTA1, CTBP2, RYR2, TRAPPC9, DOCK1, GALNTL4, HDAC4, UMODL1, ZAK and TNS3 genes). Among them, Food allergy (FA) is a current public health issue with an increasing incidence over time, suggesting potential epigenetic triggers. Nearly 8% of children have FA in the United States. 1 Food allergy can produce high alteration of the quality of life. In some cases, it may have a severe presentation with life-threatening complications, including fatal episodes of anaphylaxis. 2 There are more than 170 foods that have been reported to cause FA; among them, eight common foods (i.e., cow's milk, hen's egg, peanut, tree nuts, wheat, soy, fish and crustacean shellfish) are responsible for 90% of the reported FA CAMTA1 and RPS6KA2, and CTBP2 are involved in regulatory T cell function and Th2 cell differentiation, respectively. Gene-functional analysis revealed two enriched gene clusters involved in immune responses and protein phosphorylation. ChIP-X Enrichment Analysis 3 showed eight significant transcription factors (RXRA, ZBTB7A, ESR1, TCF3, MYOD1, CTCF, GATA3 and CBX2). Ingenuity Pathway Analysis identified canonical pathways involved, among other, in B cell development, pathogen-induced cytokine storm signalling pathway and dendritic cell maturation. Conclusion:This review highlights the involvement of epigenomic alterations of loci in Th1/Th2 and regulatory T cell differentiation in both candidate gene studies and EWAS. These alterations provide a better insight into the mechanistic aspects in FA pathogenesis and may guide the development of epigenome-based biomarkers for FA.

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Section: Resultsmentioning

confidence: 73%

Section: Literature Search Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Epigenome alterations in food allergy: A systematic review of candidate gene and epigenome‐wide association studies

Safar

Oussalah

Mayorga

et al. 2023

Clin Experimental Allergy

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“…It's confirmed that exogenous 25-OHD in vitro recovered TLR-induced antimicrobial responses (40). In Poole et al's study, a significant correlation between vitamin D and TLR2 pathways was found, indicating that vitamin D may upregulate the TLR pathway (41).…”

Section: Vitamin D Participates In the Immune Regulation Of Allergic Diseasesmentioning

confidence: 69%

A narrative review of vitamin D and food allergy in infants and children

Di¹,

Chen²

2021

Transl Pediatr

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Objective: This article summarizes the research progress on the association of vitamin D and food allergy in infants and children. Background: In recent years, food allergy seriously has affected the quality of life of children and adults. Vitamin D is known to be involved in calcium and phosphorus metabolism, and recent research has demonstrated that vitamin D can also affect the immune regulation of food allergy. Methods: The present study summarizes the research progress on the association of vitamin D and food allergy in infants and children. We searched the PubMed database to identify studies on the association of vitamin D and food allergy published between January 2003 and August 2021.Conclusions: Vitamin D in the body through a number of steps into the final formation of biological effects. The implications of postnatal vitamin D levels for food allergy may be even greater. Vitamin D can prevent the intestinal immune system from being exposed to allergens by maintaining the integrity of the mucosal barrier. Many clinical studies believe that vitamin D supplementation can improve infants' and children's food allergy, however, some show negative results or opposite results. A lot of laboratory studies have confirmed that vitamin D is involved in the immune regulation of food allergy. Evidence indicates there may be a nonlinear relationship between vitamin D and food allergy. Further researches need to be launched.

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“…Significant differences in the influence of endotoxin were shown between children with HE allergy and children with CM allergy. Some different genetic variants in immunological pathways, such as human leukocyte antigen and Toll-like receptor pathways, have been associated with each FA [ 45 , 46 , 47 ]. Another article showed that genetic background, such as CD14 polymorphisms, also affects the association between endotoxin concentration and developing eczema and FA.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Food Allergy and Endotoxin Concentration and the Toleration Status at 2 Years: The Japan Environment and Children’s Study

et al. 2023

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Changes in household endotoxin concentration may affect the prognosis of food allergy (FA), but data on the association between household endotoxin concentration and an already-developed FA are scarce. Thus, we investigated the association between environmental endotoxin exposure and tolerance to hen’s egg (HE) and cow’s milk (CM) using data from children participating in the Japan Environment and Children’s Study who had HE allergies (n = 204) and CM allergy (n = 72) in their first year of life. We grouped the endotoxin results into quartiles 1–4 (Q1–Q4). In children with HE allergy and with CM allergy, there was no significant difference in the prevalence of tolerance to HE and CM at 2 years old when comparing endotoxin levels of the children in Q1 with those in Q2, Q3, and Q4, respectively. However, subgroup analyses by the presence of eczema and causal foods revealed that children in Q1 had a lower prevalence of tolerance to foods in some subgroup analyses and lower causal allergen-specific immunoglobulin G4 levels. Although an individually based approach against endotoxin according to background characteristics, such as eczema and causal foods, is necessary, preventing excessive endotoxin removal might contribute to FA resolution in some children.

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Children with nut allergies have impaired gene expression of Toll‐like receptors pathway

Cited by 9 publications

References 34 publications

Epigenome alterations in food allergy: A systematic review of candidate gene and epigenome‐wide association studies

Epigenome alterations in food allergy: A systematic review of candidate gene and epigenome‐wide association studies

A narrative review of vitamin D and food allergy in infants and children

Relationship between Food Allergy and Endotoxin Concentration and the Toleration Status at 2 Years: The Japan Environment and Children’s Study

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