Digestomics of Cow's Milk: Short Digestion-Resistant Peptides of Casein Form Functional Complexes by Aggregation.

Jelena Radosavljević,Danijela Apostolović,Lidija Burazer,Tanja Ćirković Veličković,Marianne Van Hage,Jelena Mihailović,Marina Atanasković-Marković

doi:10.3390/foods9111576

Abstract

The aim of this study was to identify short digestion-resistant peptides (SDRPs) released by pepsin digestion of the whole cow’s milk and examine their IgE reactivity and allergenicity. Raw milk was subjected to simulated gastric digestion. SDRPs were fractionated from the digests and identified by MS. Milk SDRPs were evaluated for aggregability, propensity to compete for IgE binding with individual milk allergens, and ability to bind IgG4 from allergic and milk-tolerant individuals. The majority of milk SDRPs originated from caseins (97% of peptides) and overlapped with the known IgE epitopes of cow’s milk allergens. SDRPs competed with milk proteins for binding to human IgE and readily formed aggregates. The average peptide length was 10.6 ± 3.5 amino acids. The ability to provoke allergenic in vivo responses was confirmed by skin-prick testing (SPT) in five milk-allergic subjects. This was attributed to the peptide ability to aggregate into non-covalent complexes. SDRPs are able to induce response in SPT, but only in 50% of the sera SDRPs were able to inhibit IgG4 binding to caseins. Hence, SDRPs corresponding to the mainly continuous epitopes of milk proteins induce allergenic in vivo responses in milk-allergic subjects due to aggregation.

Highlights

Cow’s milk is a major cause of food allergy in infancy with approximately 2.5% of young children manifesting this type of allergy [1,2]
ALA wasduring attenuated in Digestion of raw milk proved that proteolysis of was attenuated
Our results proved that milk short digestion-resistant peptides (SDRPs), which corresponded to a single IgE-binding epitope in size or to only a part of an IgE-binding epitope, preserved the ability to elicit allergic response due to their aggregation propensity (Figure 4)

Summary

Introduction

Cow’s milk is a major cause of food allergy in infancy with approximately 2.5% of young children manifesting this type of allergy [1,2]. The majority of the affected children (79%) outgrow milk allergy by the age of 16 years, leaving only 1% of adult population suffering from this condition [3]. Hypoallergenic milk formulae based on extensively hydrolyzed milk proteins are proposed as alternative forms of milk that do not cause adverse reactions. The criteria introduced by European Academy for Allergy and Clinical Immunology for labelling the milk formulas as hypoallergenic relies on the clinical tolerance of proposed formula in 90% of the milk-allergic children (with 95% confidence interval) [4]. Currently there is no agreement on the molecular weight of the peptides in milk formula that can be used as a criterion for labeling formula as hypoallergenic

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