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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, Peñataro Yori, Pablo, Kukkonen, Anna Kaarina, Kuitunen, Mikael, Guterman, L Beryl, Morris, Shaun K, Pell, Lisa G, Al Mahmud, Abdullah, Ramakrishan, Girija, Heinz, Eva 
ORCID: https://orcid.org/0000-0003-4413-3756, Kirkpatrick, Beth D, Faruque, Abu Sg, Haque, Rashidul, Looney, R John, Kosek, Margaret N, Savilahti, Erkki, Omer, Saad B, Roth, Daniel E, 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, Vol 134, Issue 15, e168789.
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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).
| Item Type: | Article |
|---|---|
| Subjects: | QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 800 Biological products producing immunity |
| Faculty: Department: | Biological Sciences > Vector Biology Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1172/jci168789 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 04 Sep 2024 15:18 |
| Last Modified: | 04 Sep 2024 15:18 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/25111 |
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