Systemic Innate Immune Activation in Food Protein Induced Enterocolitis Syndrome (FPIES)

Publication date: Available online 10 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ritobrata Goswami, Ana Belen Blazquez, Roman Kosoy, Adeeb Rahman, Anna Nowak-Wegrzyn, M. Cecilia Berin
BackgroundFood protein induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy of infancy whose pathophysiology is poorly understood.ObjectivesWe set out to identify and phenotype allergen-responsive cells in peripheral blood of a cohort of subjects undergoing supervised food challenge for FPIES.MethodsWe profiled antigen-responsive cells in peripheral blood mononuclear cells by flow cytometry, and examined cells in whole blood obtained before and after challenge by CyTOF mass cytometry and RNAseq.ResultsUsing a CD154-based detection approach, we observed that milk, soy, or rice-responsive T cells, and TNFα-producing CD154+ T cells were significantly lower in those with outgrown FPIES compared to active FPIES. However, levels were within the normal range and were inconsistent with a role in the pathophysiology of FPIES. Profiling of whole blood by CyTOF demonstrated profound activation of cells of the innate immune system after food challenge, including monocytes, neutrophils, NK cells, and eosinophils. Activation was not observed in children with outgrown FPIES. We confirmed this pattern of innate immune activation in a larger cohort by RNAseq. Furthermore, we observed pan-T cell activation and redistribution from the circulation after a positive food challenge but not in those who had outgrown their FPIES.ConclusionsOur data demonstrate a compelling role of systemic innate immune activation in adverse reactions elicited by foods in FPIES. Further investigation is needed to identify the mechanism of antigen specificity of adverse reactions to foods in FPIES.

Teaser

Using blood obtained before and after food challenges for FPIES, we show that individuals with symptoms in response to challenge have activation of neutrophils, monocytes, eosinophils, and NK cells that is not observed in those who have outgrown FPIES. This novel finding places the innate immune system at the center of FPIES pathogenesis.


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