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Tolerogenic Effect Elicited by Protein Fraction Derived From Different Formulas for Dietary Treatment of Cow's Milk Allergy in Human Cells.

ABSTRACT: Several formulas are available for the dietary treatment of cow's milk allergy (CMA). Clinical data suggest potentially different effect on immune tolerance elicited by these formulas. We aimed to comparatively evaluate the tolerogenic effect elicited by the protein fraction of different formulas available for the dietary treatment of CMA. Five formulas were compared: extensively hydrolyzed whey formula (EHWF), extensively hydrolyzed casein formula (EHCF), hydrolyzed rice formula (HRF), soy formula (SF), and amino acid-based formula (AAF). The formulas were reconstituted in water according to the manufacturer's instructions and subjected to an in vitro infant gut simulated digestion using a sequential gastric and duodenal static model. Protein fraction was then purified and used for the experiments on non-immune and immune components of tolerance network in human enterocytes and in peripheral mononuclear blood cells (PBMCs). We assessed epithelial layer permeability and tight junction proteins (occludin and zonula occludens-1, ZO-1), mucin 5AC, IL-33, and thymic stromal lymphopoietin (TSLP) in human enterocytes. In addition, Th1/Th2 cytokine response and Tregs activation were investigated in PBMCs from IgE-mediated CMA infants. EHCF-derived protein fraction positively modulated the expression of gut barrier components (mucin 5AC, occludin and ZO-1) in human enterocytes, while SF was able to stimulate the expression of occludin only. EHWF and HRF protein fractions elicited a significant increase in TSLP production, while IL-33 release was significantly increased by HRF and SF protein fractions in human enterocytes. Only EHCF-derived protein fraction elicited an increase of the tolerogenic cytokines production (IL-10, IFN-?) and of activated CD4+FoxP3+ Treg number, through NFAT, AP1, and Nf-Kb1 pathway. The effect paralleled with an up-regulation of FoxP3 demethylation rate. Protein fraction from all the study formulas was unable to induce Th2 cytokines production. The results suggest a different regulatory action on tolerogenic mechanisms elicited by protein fraction from different formulas commonly used for CMA management. EHCF-derived protein fraction was able to elicit tolerogenic effect through at least in part an epigenetic modulation of FoxP3 gene. These results could explain the different clinical effects observed on immune tolerance acquisition in CMA patients and on allergy prevention in children at risk for atopy observed using EHCF.

SUBMITTER: Paparo L

PROVIDER: S-EPMC7928417 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Tolerogenic Effect Elicited by Protein Fraction Derived From Different Formulas for Dietary Treatment of Cow's Milk Allergy in Human Cells.

Paparo Lorella L Picariello Gianluca G Bruno Cristina C Pisapia Laura L Canale Valentina V Sarracino Antonietta A Nocerino Rita R Carucci Laura L Cosenza Linda L Cozzolino Tommaso T Berni Canani Roberto R

Frontiers in immunology 20210212

Several formulas are available for the dietary treatment of cow's milk allergy (CMA). Clinical data suggest potentially different effect on immune tolerance elicited by these formulas. We aimed to comparatively evaluate the tolerogenic effect elicited by the protein fraction of different formulas available for the dietary treatment of CMA. Five formulas were compared: extensively hydrolyzed whey formula (EHWF), extensively hydrolyzed casein formula (EHCF), hydrolyzed rice formula (HRF), soy form ...[more]

PMID: 33679694

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Project description:BackgroundCow's milk is a food allergen of public health importance both in the United States and globally. Its natural history and epidemiology have been most studied among infants and young children, but the public health burden it places on adults and older pediatric populations remains unclear. This study comprehensively characterizes the US population-level burden of cow's milk allergy (CMA), including its prevalence, severity, health care utilization, psychosocial impact, natural history, and other associated factors-including ability to tolerate extensively heated milk products-within a large, nationally-representative survey sample of US households.MethodsA cross-sectional survey was administered via web and telephone. Population level inference was based on data collected from participants recruited from National Opinion Research Center (NORC) at the University of Chicago's probability-based AmeriSpeak panel. Established dual-sample complex survey calibration methods were used to augment this sample with additional participants recruited through Survey Sampling International to increase the precision of the resulting estimates. In total, surveys were administered to a nationally representative sample of 51 819 US households from October 1, 2015, through September 31, 2016. Self-report responses from 40 453 adults and parent-proxy report for 38 408 children were analyzed.ResultsAnalyzing survey responses from 78 851 individuals, an estimated 4.7% (95% CI, 4.4%-4.9%) of the US population reported current CMA, whereas 1.9% (95% CI, 1.8%-2.1%) met symptom-report criteria for convincing IgE-mediated allergy. An estimated 0.9% (95% CI, 0.8%-1.0%) had CMA that met convincing symptom-report criteria and was physician diagnosed. Female and White respondents were more likely to report outgrowing CMA relative to males and those reporting other races and ethnicities. Individuals with CMA who reported tolerance to baked milk products were less likely to report severe reaction histories (33.5% vs 42.7%; p = .03), a lifetime history of food allergy-related emergency department visits (43.4% vs. 55.8%; p = .005), and treating a milk-allergic reaction with epinephrine (10.6 vs. 18.9%; p = .003). These individuals also exhibited less psychosocial burden on the validated Food Allergy Independent Measure (FAIM) than their counterparts with CMA who were allergic to baked forms of milk.ConclusionThese data indicate a discrepancy in reported rates of allergy to cow's milk among the US general population ranging from approximately 1 in 20 with reported CMA to fewer than 1 in 50 with physician-confirmed CMA. However, they suggest a substantial population-level burden of CMA, including substantial healthcare utilization, psychosocial burden and nutritional impacts-particularly among the approximately 30% of individuals with CMA who cannot tolerate baked forms of milk.

Dataset Information

Tolerogenic Effect Elicited by Protein Fraction Derived From Different Formulas for Dietary Treatment of Cow's Milk Allergy in Human Cells.

Publications

Tolerogenic Effect Elicited by Protein Fraction Derived From Different Formulas for Dietary Treatment of Cow's Milk Allergy in Human Cells.

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