Abstract

Food allergy is a collective term for several immune-mediated responses to food. IgE-mediated food allergy is the best-known subtype. The patients present with a marked diversity of clinical profiles including symptomatic manifestations, threshold reactivity and reaction kinetics. In-vitro predictors of these clinical phenotypes are evasive and considered as knowledge gaps in food allergy diagnosis and risk management. Peanut allergy is a relevant disease model where pioneer discoveries were made in diagnosis, immunotherapy and prevention. This review provides an overview on the immune basis for phenotype variations in peanut-allergic individuals, in the light of future patient stratification along emerging omic-areas. Beyond specific IgE-signatures and basophil reactivity profiles with established correlation to clinical outcome, allergenomics, mass spectrometric resolution of peripheral allergen tracing, might be a fundamental approach to understand disease pathophysiology underlying biomarker discovery. Deep immune phenotyping is thought to reveal differential cell responses but also, gene expression and gene methylation profiles (eg, peanut severity genes) are promising areas for biomarker research. Finally, the study of microbiome-host interactions with a focus on the immune system modulation might hold the key to understand tissue-specific responses and symptoms. The immune mechanism underlying acute food-allergic events remains elusive until today. Deciphering this immunological response shall enable to identify novel biomarker for stratification of patients into reaction endotypes. The availability of powerful multi-omics technologies, together with integrated data analysis, network-based approaches and unbiased machine learning holds out the prospect of providing clinically useful biomarkers or biomarker signatures being predictive for reaction phenotypes.

Highlights

  • Reviewed by: Wenming Zhang, Stanford University, United States Johanna Smeekens, University of North Carolina at Chapel Hill, United States

  • Decreased microbial richness associated with Peanut allergy (PA) Increased alpha-diversity in low responsive individuals Bacteroidales, especially Bacteroides fragili increased in PA, Clostridium sp increased in low threshold; high Oscillosiraceae sp, Lachnospiraceae sp, Ruminococcaceae sp, Frimicutes sp and Bacteroides sp correlating with low threshold reactivity Clostridiales abundance decreased in PA, potentially leading to a decrease in protective ROR-gt+ iTreg cell populations Local class switch resulting in IgE+ B cell counts correlating with serum sIgE-titers; at the gut microbiome interface, local IgE-reservoir for mast cell FcεRI-coating and candidate factors triggering clinical reactivity profiles

  • Deciphering the immunological response to food proteins shall enable the stratification of patients into reaction endotypes, for advanced understanding of their phenotypic heterogeneity

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Summary

Pathophysiological Basis

IgE-mediated FA is considered as an epithelial barrier disease, resulting from food protein uptake via disrupted barriers (gastrointestinal tract, skin, lung) which in turn, leads to an immune dysregulation, and food proteins being recognized as hostile invaders in a T helper type 2 (Th2)skewed immune response [3, 8]. Epithelium-derived danger signals and pro-inflammatory cytokines, including interleukin 25 (IL-25) and IL-33, orchestrate the activation and expansion of type 2 innate lymphoid cells (ILC2) and dendritic cells (DCs) [9,10,11]. Those activated DCs promote again the differentiation of naive T cells into a Th2 phenotype cells. Food antigens undergo molecular interactions with cell-bound IgE-antibodies via specific epitopes, leading to cell activation and mediator release via crosslinking of FceRI-bound IgE. Released inflammatory mediators, including histamine, prostaglandins, tryptase, and platelet-activating factor (PAF), contribute to the clinical symptoms

Clinical Features
Food Allergens
Food Allergy Diagnosis
Molecular Endotyping
Molecular endotyping
Serum IgE to peanut epitopes
Immunological endotyping
Multimodal omics
Fecal microbiome
Multimodal Omics
Commensal Endotyping
PERSPECTIVE TOWARD NEW INTEGRATIVE APPROACHES
Findings
AUTHOR CONTRIBUTIONS
Full Text
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