Determining the Heterogeneity of Maternal Milk Immunoglobulin A Antibacterial Response

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Submission ID :
ESPR209
Submission Type
Submission Topic
Abstract: :

Background: Necrotizing enterocolitis (NEC) is a disease of preterm infants, characterized by damage to the intestinal tract. NEC affects ~7% of preterm infants and has a mortality rate of 30%. The etiology of NEC is not well understood, but it is associated with invasion of the intestine by bacteria. Feeding infants with maternal milk has reduced NEC, but it is not 100% protective. Immunoglobulin A (IgA) antibodies are an antibacterial mechanism found in maternal milk. In the days prior to the development of NEC, affected infants have decreased IgA-bound bacteria in their intestine. We hypothesize that differences in the IgA repertoire between different mothers affect the antibacterial function of maternal milk.

Objective: 
We will test the hypothesis that the maternal IgA repertoire of different mothers is heterogeneous.

Design/Methods: 
We have carried out four studies. First, we compared IgA samples collected from term maternal milk captured from 18 donors. Second, we compared preterm maternal milk captured from 8 donors. Third, we collected colostrum, transitional, and mature maternal milk samples from 10 donors and tested whether IgA shifted over time. Fourth, we compared IgA from pasteurized and unpasteurized milk samples from 5 donors and measured the effect on the antibacterial repertoire. IgA was isolated, concentrated with peptide-M columns, quantified, and normalized. Maternal milk-derived IgA was then used to stain the arrayed bacterial cultures followed by detection with an anti-human IgA antibody and flow cytometry (Figure 1). IgA binding data was compiled and compared in a heat map.

Results: 
We observed a significant variation in IgA binding between different donors, particularly amongst bacterial strains from Enterobacteriaceae, where the binding of IgA was stronger in some donors compared to others. Longitudinally captured samples grouped together, indicating that the IgA repertoire of one mother is stable. We also saw that there was strain level variation in IgA binding within a donor. For example, some donors bind only some strains of Escherichia coli (Figure 2). Lastly, the antibacterial repertoire remained stable following pasteurization.

Conclusion(s): 
We have described a novel technique for the evaluation of the antibacterial IgA repertoire of maternal milk. We have shown that the IgA antibacterial repertoire was unique to each donor, maintained over time, and that it shows strain-level specificity. Together our data indicates that the maternal milk IgA repertoire may be dependent upon the individualized immune history of the maternal donor. We propose that targeting pre-tested donor samples to the most at-risk infants or augmenting maternal milk such that it binds the bacteria best associated with NEC may be prophylactic to the development of disease.

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UPMC - Children's Hospital of Pittsburgh
University of Pittsburgh Medical Center
University of Pittsburgh Medical Center
University of Pittsburgh Medical Center
University of Pittsburgh

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