Abstract
BackgroundFood Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow’s milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.MethodsChildren with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry.ResultsNine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients.ConclusionsIn CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease.
Highlights
Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy
Population Nine out twelve of the cow’s milk (CM)-FPIES children recruited had a positive challenge on the day of the open food challenge (OFC), reacting at 45 mL of raw CM or less, with 1 having a hypovolemic shock
Nine children with CM-FPIES and six children with IgE-Cow’s milk allergy (CMA) were included in the present study
Summary
Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. Food Protein-Induced Enterocolitis Syndrome (FPIES) is a food allergy affecting predominantly infants, with cow’s milk (CM) being the most common causative food. Symptoms depend on frequency of food exposure [1, 2]. Symptoms improve after CM exclusion and re-exposure leads to a typical acute digestive form including repetitive protracted vomiting starting 1–4 h after CM ingestion, often accompanied by pallor and lethargy [3]. Resolution of FPIES occurs at different ages depending on the food and the geographical regions considered, with children presenting IgE sensitization at higher risk of a protracted course [4,5,6,7]
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