Presence of functional, autoreactive human milk‐specific IgE in infants with cow's milk allergy

Abstract

Summary 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.

Mother-to-Child Transmission of HTLV-1 Epidemiological Aspects, Mechanisms and Determinants of Mother-to-Child Transmission

“…Cell free virions have not been detected so far in breast milk, thus the potential source of infection in breast milk may come from infected cells, such as lymphocytes, macrophages, or breast epithelial mammary cells. Since it has been estimated that breastfed children ingest an average of 10 8 leucocytes a day, considering prolonged breastfeeding [ 34 , 35 ], infected lymphocytes could provide a strong source of infection in milk [ 36 ]. HTLV-1 infected mononuclear cells can be found in the milk from seropositive mothers during early lactation [ 23 , 37 ].…”

Development of natural tolerance and induced desensitization in cow’s milk allergy

“…Sensitization to bovine serum albumin (BSA) is associated with allergic symptoms to both CM and beef (15). In cases where CMA affects an infant who is exclusively breastfed, the eliciting CM exposure may arise through breast milk or cutaneous exposure, and CMA may be sustained by cross‐reactivity to proteins in human breast milk (16).…”

Importance of maternal diet in the training of the infant's immune system during gestation and lactation

“…It can be hypothesized that, like seen in immunotherapy approaches (Hussey Freeland et al 2016), the initial exposure with low dosages that over time increase, will result in a tolerogenic response instead of the onset of an allergic response. Cases of allergic manifestations towards endogenous human milk proteins, purportedly through crossreactivity with structurally similar cow's milk proteins, have been reported, but seem to be excessively rare (Jarvinen et al 2012;Makinen-Kiljunen and Plosila 2004).…”