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Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG
Joseph J. Campo, … , William A. Petri Jr., Kirsi M. Järvinen
Joseph J. Campo, … , William A. Petri Jr., Kirsi M. Järvinen
Published August 1, 2024
Citation Information: J Clin Invest. 2024;134(15):e168789. https://doi.org/10.1172/JCI168789.
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Clinical Research and Public Health Infectious disease Article has an altmetric score of 144

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

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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.FUNDING Bill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).

Authors

Joseph J. Campo, Antti E. Seppo, Arlo Z. Randall, Jozelyn Pablo, Chris Hung, Andy Teng, Adam D. Shandling, Johnathon Truong, Amit Oberai, James Miller, Najeeha Talat Iqbal, Pablo Peñataro Yori, Anna Kaarina Kukkonen, Mikael Kuitunen, L. Beryl Guterman, Shaun K. Morris, Lisa G. Pell, Abdullah Al Mahmud, Girija Ramakrishan, Eva Heinz, Beth D. Kirkpatrick, Abu S.G. Faruque, Rashidul Haque, R. John Looney, Margaret N. Kosek, Erkki Savilahti, Saad B. Omer, Daniel E. Roth, William A. Petri Jr., Kirsi M. Järvinen

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Figure 8

Association of human milk IgA with infection in breastfed infants.

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Association of human milk IgA with infection in breastfed infants.
(A) A...
(A) Association of IgA binding to each pathogen for infants subsequently infected with the specific pathogen or not. The log odds from logistic regression of enteric (left) or respiratory (right) infection with increasing IgA binding (x axis) in infants during 1 year and 6 months of follow up, respectively, are shown with the inverse log10 P value (y axis). Associations significant after correction for the FDR are shown in colored triangles. Samples analyzed for diarrheal illness were from the Bangladesh PROVIDE cohort (n = 256) and for respiratory illness were from the Bangladesh MDIG cohort (n = 246). (B) Survival curves of 256 infants from the PROVIDE cohort for enteric pathogens detected by PCR. (C) Hazard ratios of infants during the first year of life divided into the top and bottom halves of mothers’ milk IgA responses for each antigen that was reactive in at least 10% of PROVIDE cohort women. Milk samples included were from mothers with infants that subsequently had pathogen-specific infection. Values below 1.0 represent lower risk of infection in the top half of milk IgA responses compared with the bottom half. For unadjusted P values less than 0.05, antigens were colored (otherwise grey), FDR-adjusted P values less than 0.05 were plotted as triangles. (D and E) Representative Rotavirus A antigen (D) and Campylobacter jejuni antigen (E) corresponding to the samples included in the models shown in the volcano plot (C). The risk tables show the number at risk during 100-day intervals. The Rotavirus A VP4 outer capsid protein is representative of antibodies associated with longer time to infection, while the C. jejuni PEB4 major antigenic peptide (Cj0596) represents antibodies associated with a shorter time to infection. HR, Cox model coefficient for the hazard ratio; CI, confidence interval; P, log-rank test P value; FDR P, adjusted P value.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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