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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:135

Article

Martino, David^1,2,4  Dang, Thanh^1,2  Sexton-Oates, Alexandra²  Prescott, Susan^1,3  Tang, Mimi L. K.^1,2,4,5  Dharmage, Shyamali^1,2,6  Gurrin, Lyle^1,2,6  Koplin, Jennifer^1,2,6  Ponsonby, Anne-Louise^1,2,4  Allen, Katrina J.^1,2,4,7  Saffery, Richard^2,4 

[1] Murdoch Childrens Res Inst, Ctr Food & Allergy Res, Parkville, Vic, Australia

[2] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia

[3] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia

[4] Univ Melbourne, Dept Paediat, Melbourne, Vic 3010, Australia

[5] Royal Childrens Hosp, Dept Allergy & Immunol, Parkville, Vic 3052, Australia

[6] Univ Melbourne, Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia

[7] Univ Manchester, Inst Inflammat & Repair, Manchester M13 9PL, Lancs, England

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

DOI  :  10.1016/j.jaci.2014.12.1933

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free