Dataset Information

Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.

ABSTRACT: Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity; however, heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. Surprisingly, we also observed intradonor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the antibacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the antibacterial BrmIgA reactivity displays interindividual heterogeneity but intraindividual stability. These findings have important implications for how breast milk shapes the development of the preterm infant microbiota and protects against necrotizing enterocolitis.

SUBMITTER: Johnson-Hence CB

PROVIDER: S-EPMC10354535 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.

Johnson-Hence Chelseá B CB Gopalakrishna Kathyayini P KP Bodkin Darren D Coffey Kara E KE Burr Ansen H P AHP Rahman Syed S Rai Ali T AT Abbott Darryl A DA Sosa Yelissa A YA Tometich Justin T JT Das Jishnu J Hand Timothy W TW

The Journal of experimental medicine 20230718 8

Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity; however, heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity b ...[more]

PMID: 37462916

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Project description:BackgroundIn our previous study about 75% of children with cow's milk allergy tolerated baked milk products, which improved their prognosis and quality of life.ObjectiveWe sought to identify biomarkers of varying degrees of clinical tolerance among a cohort of children with cow's milk allergy.MethodsOne hundred thirty-two subjects were initially classified as baked milk-reactive, baked milk-tolerant, or having "outgrown milk allergy" based on the results of oral food challenges. The baked milk-tolerant group was then divided into 3 groups based on the amount and degree of heat-denatured milk protein that they could tolerate. Serum was analyzed for allergen-specific IgE and IgG(4) levels, basophil reactivity was assessed in whole blood stimulated with serial 10-fold dilutions of milk protein, and skin prick tests (SPTs) were performed to commercial milk extract. Activated basophils were defined by using flow cytometry as CD63(bright)CD203c(+)CD123(+)HLA-DR(dim/-)CD41a(-)lineage(-). Data were analyzed by using the Jonckheere-Terpstra test.ResultsSignificant differences across the 5 clinical groups were seen for median casein- and milk-specific IgE levels, casein-specific IgG(4) levels, and casein IgE/IgG(4) ratios; milk-specific to nonspecific basophil activation ratio, median basophil reactivity, and spontaneous basophil activation (CD203c expression after stimulation with RPMI); and milk SPT wheal diameters. Casein- and milk-specific IgE level, milk-specific basophil reactivity, and milk SPT wheal diameter are all significantly greater among patients with milk allergy who react to baked milk than among those who tolerate it.ConclusionsThe majority of patients with milk allergy are able to tolerate some forms of baked milk in their diets. Different phenotypes of children with cow's milk allergy can be distinguished by casein- and milk-specific IgE levels, milk-specific basophil reactivity, and milk SPT mean wheal diameters. Spontaneous basophil activation is greater among patients with more severe clinical milk reactivity.

Dataset Information

Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.

Publications

Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.

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