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Updated: May 27, 2026

Humanized Mediator Release Assay as a Read-Out for Allergen Potency
Published on: June 29, 2021
Presence of functional, autoreactive human milk-specific IgE in infants with cow's milk allergy
K M Järvinen1, L Geller, R Bencharitiwong
1Division of Pediatric Allergy & Immunology, The Mount Sinai School of Medicine, New York, NY 10029-6574, USA. kirsi.jarvinen-seppo@mssm.edu
Background:
Occasionally, exclusively breastfed infants with cow's milk allergy (CMA) remain symptomatic despite strict maternal milk avoidance.
Objective:
To determine whether or not persistence of symptoms could be due to sensitization against endogenous human milk proteins with a high degree of similarity to bovine allergens.
Methods:
Ten peptides representing known bovine milk IgE-binding epitopes [α-lactalbumin (ALA), β- and κ-casein] and the corresponding, highly homologous human milk peptides were labelled with sera from 15 breastfed infants with CMA, aged 3 weeks to 12 months, and peptide (epitope)-specific IgE antibodies were assessed. Nine of the 15 breastfed infants became asymptomatic during strict maternal avoidance of milk and other major food allergens; six infants remained symptomatic until weaned. Ten older children, aged 5-15 years, with CMA were also assessed. The functional capacity of specific IgE antibodies was assessed by measuring β-hexosaminidase release from rat basophilic leukaemia cells passively sensitized and stimulated with human and bovine ALA.
Results:
A minimum of one human milk peptide was recognized by IgE antibodies from 9 of 15 (60%) milk-allergic infants, and the majority of older children with CMA. Genuine sensitization to human milk peptides in the absence of IgE to bovine milk was occasionally seen. There was a trend towards specific IgE being detected to more human milk peptides in those infants who did not respond to the maternal milk elimination diet than in those who did (P = 0.099). Functional IgE antibody to human ALA was only detected in infants not responding to the maternal diet.
Conclusions And Clinical Relevance:
Endogenous human milk epitopes are recognized by specific IgE from the majority of infants and children with CMA. Such autoreactive, human milk-specific IgE antibodies appear to have functional properties in vitro. Their role in provoking allergic symptoms in infants exclusively breastfed by mothers strictly avoiding dietary milk remains unclear.
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