Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG

Campo, Joseph J. and Seppo, Antti E. and Randall, Arlo Z. and Pablo, Jozelyn and Hung, Chris and Teng, Andy and Shandling, Adam D. and Truong, Johnathon and Oberai, Amit and Miller, James and Iqbal, Najeeha Talat and Yori, Pablo Peñataro and Kukkonen, Anna Kaarina and Kuitunen, Mikael and Guterman, L. Beryl and Morris, Shaun K. and Pell, Lisa G. and Al Mahmud, Abdullah and Ramakrishan, Girija and Heinz, Eva and Kirkpatrick, Beth D. and Faruque, Abu S.G. and Haque, Rashidul and Looney, R. John and Kosek, Margaret N. and Savilahti, Erkki and Omer, Saad B. and Roth, Daniel E. and Petri, William A. and Järvinen, Kirsi M. (2024) Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG. Journal of Clinical Investigation, 134 (15). e168789. ISSN 0021-9738 (https://doi.org/10.1172/JCI168789)

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Abstract

BACKGROUND. The use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations. METHODS. Using multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens. RESULTS. The antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli “EPEC”, Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection. CONCLUSION. This comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.

ORCID iDs

Campo, Joseph J., Seppo, Antti E., Randall, Arlo Z., Pablo, Jozelyn, Hung, Chris, Teng, Andy, Shandling, Adam D., Truong, Johnathon, Oberai, Amit, Miller, James, Iqbal, Najeeha Talat, Yori, Pablo Peñataro, Kukkonen, Anna Kaarina, Kuitunen, Mikael, Guterman, L. Beryl, Morris, Shaun K., Pell, Lisa G., Al Mahmud, Abdullah, Ramakrishan, Girija, Heinz, Eva ORCID logoORCID: https://orcid.org/0000-0003-4413-3756, Kirkpatrick, Beth D., Faruque, Abu S.G., Haque, Rashidul, Looney, R. John, Kosek, Margaret N., Savilahti, Erkki, Omer, Saad B., Roth, Daniel E., Petri, William A. and Järvinen, Kirsi M.;
CORE (COnnecting REpositories)