Breast milk IgA to foods has different epitope specificity than serum IgA—Evidence for entero‐mammary link for food‐specific IgA?

Abstract

These findings support the concept that mother's milk has a distinct antifood antibody repertoire when compared to the antibody repertoire of the peripheral blood. Increased binding of serum epitope-specific IgA to CM in mothers of infants with CMA may reflect inherited systemic immunogenicity of CM proteins in these families, although specific IgA in breast milk was not proportionally up-regulated.

Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19

“…The B cells that ultimately produce milk sIgA/sIgM originate mainly from the GALT, known as the entero-mammary link, with some proportion originating from other mucosa such as the respiratory system (1,19,20). Evidence supporting this enteromammary link include the finding that mammary gland B cells display an adhesion receptor profile matching that found on GALT B cells, and that milk sIgA exhibits high reactivity for enteric antigens compared to blood (21)(22)(23)(24). In fact, PRM/Alf mice (possessing elongated intestinal tracts) have been shown to exhibit increased gut-derived B cells in the mammary gland and increased milk sIgA concentration compared to wild type mice (25).…”

Immunologically Active Components in Human Milk and Development of Atopic Disease, With Emphasis on Food Allergy, in the Pediatric Population

“…Mucosal IgAs are produced by plasma cells in the gut lamina propria and are transported across epithelial cells by the polymeric immunoglobulin receptor (pIgR) ( 83 ). Human milk IgA is produced by mammary gland B cells that have migrated from the mother's intestine via the “enteromammary link” ( 84 , 85 ), as shown in animal studies ( 86 – 89 ). This is controlled by the mucosal vascular addressin MadCAM-1 or mucosa-associated epithelial chemokine CCL28, which interacts with the gut homing receptor α 4 β 7 integrin ( 90 ) and mucosa-associated CCR10 ( 91 ).…”

“…Consistent with this, in a rabbit model either oral or inhaled RSV resulted in RSV-IgA production in milk, bronchial and enteral secretions, whereas systemic immunization did not ( 92 ). Studies in humans ( 93 ) showed that oral immunization in women resulted in an increase in plasma cells in milk, but not in saliva or serum, ( 85 ). This forms the hypothesis that human milk IgA reflects the antigenic exposure of the mother's gut to dietary proteins as well.…”

Ovomucoid epitope‐specific repertoire of IgE, IgG4, IgG1, IgA1, and IgD antibodies in egg‐allergic children

“…31 However, recent research in food allergy has been mostly focused on understanding epitope-specific repertoire of IgE and IgG 4 , with only a limited number of studies addressing epitope specificity of IgG 1 , IgA, and IgD. 41,42 We have previously presented a bead-based epitope assay that is highly reliable and sensitive for detecting milk 43,44 and peanut 45…”