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

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 4

Pathogen-specific IgA and IgG breadth scores in mature milk and colostrum by economic classification.

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Pathogen-specific IgA and IgG breadth scores in mature milk and colostru...
The box plots show comparisons of mature milk and colostrum IgA and IgG breadth scores (row headers), defined as the proportion of seropositive (normalized signal ≥ 1.0) antigens per pathogen for each individual (e.g., 20 of 80 positive responses = 0.25 breadth score). The column headers indicate the type of pathogens displayed in each column: enteric, respiratory, and sepsis-related pathogens. Rotavirus and Adenovirus 40/41 were omitted from the enteric pathogens column due to low numbers of reactive antigens. The x axes show each pathogen grouped by HIC (orange boxes) and LMIC (blue boxes) classifications. The y-axes show the IgA or IgG breadth scores on a logarithmic scale with the boxes representing the median and interquartile range. Significant differences by Wilcoxon’s rank sum tests are shown by blue asterisks below each pathogen: *P ≤ 0.05, ** P ≤ 0.005, ** P* ≤ 0.0005. Mature milk samples (n = 438) were included from the latest sample collection for each cohort and were at least 6 weeks postpartum. Colostrum samples (n = 64) were collected in the first 5 days. E. coli, diarrheagenic types EAEC, EPEC and ETEC; RSV, respiratory syncytial virus; GBS, group B Streptococcus.