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J Allergy Clin Immunol. 2015 May;135(5):1319-28.e1-12. doi: 10.1016/j.jaci.2014.12.1933. Epub 2015 Feb 10.

Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.

Author information

1
Centre for Food and Allergy Research, Murdoch Childrens Research Institute, Parkville, Australia; Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia; University of Melbourne Department of Paediatrics, Melbourne, Australia; In-FLAME, the International Inflammation Network, World Universities Network (WUN), Perth, Australia.
2
Centre for Food and Allergy Research, Murdoch Childrens Research Institute, Parkville, Australia; Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia.
3
Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia.
4
Centre for Food and Allergy Research, Murdoch Childrens Research Institute, Parkville, Australia; School of Paediatrics and Child Health, University of Western Australia, Perth, Australia; In-FLAME, the International Inflammation Network, World Universities Network (WUN), Perth, Australia.
5
Centre for Food and Allergy Research, Murdoch Childrens Research Institute, Parkville, Australia; Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia; University of Melbourne Department of Paediatrics, Melbourne, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Australia.
6
Centre for Food and Allergy Research, Murdoch Childrens Research Institute, Parkville, Australia; School of Population and Global Health, University of Melbourne, Melbourne, Australia.
7
Centre for Food and Allergy Research, Murdoch Childrens Research Institute, Parkville, Australia; Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia; University of Melbourne Department of Paediatrics, Melbourne, Australia.
8
Centre for Food and Allergy Research, Murdoch Childrens Research Institute, Parkville, Australia; Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia; University of Melbourne Department of Paediatrics, Melbourne, Australia; In-FLAME, the International Inflammation Network, World Universities Network (WUN), Perth, Australia; Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom. Electronic address: Katie.Allen@rch.org.au.
9
Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia; University of Melbourne Department of Paediatrics, Melbourne, Australia.

Abstract

BACKGROUND:

The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity.

OBJECTIVE:

We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes.

METHODS:

Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA.

RESULTS:

Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%.

CONCLUSION:

DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays.

KEYWORDS:

DNA methylation profiling; Food allergy; Infinium; allergy epigenetics; biomarkers; epigenetic epidemiology; epigenetics; methylation profiling; shrunken centroids

PMID:
25678091
DOI:
10.1016/j.jaci.2014.12.1933
[Indexed for MEDLINE]

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