Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop

Bunyavanich, Supinda; Becker, Patrice M.; Altman, Matthew C.; Lasky-Su, Jessica; Ober, Carole; Zengler, Karsten; Berdyshev, Evgeny; Bonneau, Richard; Chatila, Talal; Chatterjee, Nilanjan; Chung, Kian Fan; Cutcliffe, Colleen; Davidson, Wendy; Dong, Gang; Fang, Gang; Fulkerson, Patricia; Himes, Blanca E.; Liang, Liming; Mathias, Rasika A.; Ogino, Shuji; Petrosino, Joseph; Price, Nathan D.; Schadt, Eric; Schofield, James; Seibold, Max A.; Steen, Hanno; Wheatley, Lisa; Zhang, Hongmei; Togias, Alkis; Hasegawa, Kohei

doi:10.1016/j.jaci.2024.01.014

Cited by 4 publications

(2 citation statements)

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“…PNOIT: Pediatric participants (aged [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] enrolled in an open-label interventional peanut OIT trial, which involved the administration of gradually increasing doses of peanut allergen in order to decrease patients' sensitivity to peanut allergen (ClinicalTrials.gov ID NCT01324401). 28 Participants underwent a buildup phase where they were given incrementally increasing amounts of peanut protein, followed by a maintenance period with a daily dose of 4 grams.…”

Section: Methodsmentioning

confidence: 99%

“…10,11 Studies support the utility of metabolomic analyses in identifying pathways associated with food allergy, while several investigations have explored the evolution of metabolomic profiles on other types of aeroallergen sublingual and subcutaneous immunotherapy. 9,[12][13][14][15][16][17][18][19][20][21] To date, one study has examined water soluble metabolites in the stool in the setting of food immunotherapy, and none have studied the plasma metabolome in humans. 22 .…”

Section: Introductionmentioning

confidence: 99%

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Metabolomics of IgE-Mediated Food Allergy and Oral Immunotherapy Outcomes based on Metabolomic Profiling

Virkud,

Styles,

Kelly

et al. 2024

Preprint

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BackgroundThe immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.ObjectiveTo identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multi-ethnic cohorts and responses to OIT.MethodsUntargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N=384), a Costa Rican cohort of children with asthma (N=1040), and a peanut OIT trial (N=20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterwards). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.ResultsCompared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q=2.4×10−20) and linoleic acid derivatives (q=3.8×10−5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q=4.1×10−8), eicosanoids (q=7.9×10−7), and histidine pathways (q=0.015). In particular, the bile acid lithocholate (4.97[1.93,16.14], p=0.0027), the eicosanoid leukotriene B4 (3.21[1.38,8.38], p=0.01), and the histidine metabolite urocanic acid (22.13[3.98,194.67], p=0.0015) were higher in SU.ConclusionsWe observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.Key Messages–Compared with unaffected controls, children with food allergy demonstrated higher levels of bile acids and distinct histidine/urocanic acid profiles, suggesting a potential role of these metabolites in food allergy.–In participants receiving oral immunotherapy for food allergy, those who were able to maintain tolerance-even after stopping therapyhad lower overall levels of bile acid and histidine metabolites, with the exception of lithocholic acid and urocanic acid, two metabolites that have roles in T cell differentiation that may increase the likelihood of remission in immunotherapy.Capsule summaryThis is the first study of plasma metabolomic profiles of responses to OIT in individuals with IgE-mediated food allergy. Identification of immunomodulatory metabolites in allergic tolerance may help identify mechanisms of tolerance and guide future therapeutic development.

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