Dataset Information

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow's milk.

ABSTRACT:

Background

Food 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.

Methods

Children 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.

Results

Nine 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.

Conclusions

In 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.

SUBMITTER: Adel-Patient K

PROVIDER: S-EPMC6161449 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow's milk.

Adel-Patient Karine K Lezmi Guillaume G Castelli Florence Anne FA Blanc Sibylle S Bernard Hervé H Soulaines Pascale P Dumond Pascale P Ah-Leung Sandrine S Lageix Florence F de Boissieu Delphine D Cortes-Perez Naima N Hazebrouck Stéphane S Fenaille François F Junot Christophe C Dupont Christophe C

Clinical and translational allergy 20180928

<h4>Background</h4>Food 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.<h4>Methods</h4>Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), bot ...[more]

PMID: 30275944

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Project description:Importance:Cow's milk formula (CMF) is used to supplement breastfeeding (BF) at birth without clear clinical evidence to support the practice. Objective:To determine whether avoiding supplementation with CMF at birth can decrease risks of sensitization to cow's milk protein and/or clinical food allergy, including cow's milk allergy (CMA), overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels. Design, Setting, and Participants:The Atopy Induced by Breastfeeding or Cow's Milk Formula (ABC) trial, a randomized, nonblinded clinical trial, began enrollment October 1, 2013, and completed follow-up May 31, 2018, at a single university hospital in Japan. Participants included 330 newborns at risk for atopy; of these, 312 were included in the analysis. Data were analyzed from September 1 through October 31, 2018. Interventions:Immediately after birth, newborns were randomized (1:1 ratio) to BF with or without amino acid-based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with CMF (?5 mL/d) from the first day of life to 5 months of age (BF plus CMF group). Main Outcomes and Measures:The primary outcome was sensitization to cow's milk (IgE level, ?0.35 allergen units [UA]/mL) at the infant's second birthday. Secondary outcomes were immediate and anaphylactic types of food allergy, including CMA, diagnosed by oral food challenge test or triggered by food ingestion, with food-specific IgE levels of at least 0.35 UA/mL. Subgroup analysis was prespecified by tertiles of serum 25(OH)D levels at 5 months of age. Results:Of the 312 infants included in the analysis (160 female [51.3%] and 152 male [48.7%]), 151 of 156 (96.8%) in the BF/EF and BF plus CMF groups were followed up until their second birthday. The primary outcome occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk [RR], 0.52; 95% CI, 0.34-0.81). The middle tertile of the 25(OH)D subgroup, but not the low and high tertiles, had a significant interaction with the intervention (RR, 0.19; 95% CI, 0.07-0.50; P?=?.02). The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]; RR, 0.20; 95% CI, 0.07-0.57) and anaphylactic (1 [0.7%] vs 13 [8.6%]; RR, 0.08; 95% CI, 0.01-0.58) types. Conclusions and Relevance:The evidence suggests that sensitization to cow's milk and food allergy, including CMA and anaphylaxis, are primarily preventable by avoiding CMF supplementation for at least the first 3 days of life. Trial Registration:http://umin.ac.jp Identifier: UMIN000011577.

Project description:BackgroundCurrent guidelines emphasize early introduction to potentially allergenic foods, but the optimal timing, amount, and exposure routes for foods other than peanut are not well-established. Cow's milk is often the first allergenic food introduced through infant formulas.ObjectiveTo examine timing of cow's milk protein introduction (CMPI), including interaction with formula supplementation after delivery, in relation to reported cow's milk adverse reactions throughout childhood.MethodsAmong children in the Boston, Mass-area Project Viva cohort, we assessed timing of CMPI (<2 weeks, 2 weeks-<6 months, ≥6 months) with questionnaires administered in infancy. Outcomes were (1) parent-reported cow's milk adverse reactions via annual questionnaires from age 2 to 13 years (n = 1298) and (2) milk sensitization (n = 505) and IgE-mediated milk allergy (n = 491) at age approximately 8 years. We used multivariable logistic regression models adjusted for parental atopy history, delivery mode, gestational age at delivery, child race, and census tract median household income, and investigated effect modification by ever/never breast-fed status and formula supplementation in the delivery hospital.ResultsA total of 32% were introduced to cow's milk protein at age less than 2 weeks, 38% at age 2 weeks to less than 6 months, and 30% at age 6 months or more. Compared with children with CMPI at age less than 2 weeks, children with CMPI at age 6 months or more had a higher risk of cow's milk adverse reaction at age 2 to 5 years (odds ratio, 2.4 [1.2-4.7]). Children given formula after delivery + CMPI at age less than 2 weeks had the lowest risk overall. Among children not given formula after delivery, CMPI at age 2 weeks to 6 months appeared most protective. Results were similar among ever-breast-fed children. Timing of CMPI was not associated with milk sensitization or IgE-mediated milk allergy in mid-childhood.ConclusionsEarly, consistent cow's milk exposure appears protective against adverse reactions to cow's milk.

Dataset Information

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow's milk.

Background

Methods

Results

Conclusions

Publications

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow's milk.

Similar Datasets

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