Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG
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
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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Clinical Research and Public Health Infectious disease

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 7

Pathogen-specific IgA and IgG concentrations in mature milk and colostrum by economic region.

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Pathogen-specific IgA and IgG concentrations in mature milk and colostru...
Scatter plots show IgA or IgG concentrations for each of the reactive antigens from enteric, respiratory, and sepsis-related pathogens (row headers) in mature milk and colostrum (column headers). Antigens classified as “reactive” were those having a median value ≥ 1.0 across the entire study population. Each point represents the mean normalized signal intensity for an individual antigen, colored by pathogen (row legends); solid triangles represent antigens with significant differential reactivity between cohorts by t tests after correction for the FDR. Y axes show means for samples from LMICs, and x axes show means for samples from HICs. The countries included in each plot are listed along the y-axis (LMICs) and x-axis (HICs) with sample sizes in parentheses. The solid diagonal line represents the line of identity (i.e., similar mean signal intensity between LMICs and HICs). Mature milk samples were those from the latest sample collection for each cohort and were at least 6 weeks postpartum. Colostrum samples were collected at 0 weeks. E. coli, diarrheagenic types EAEC, EPEC and ETEC; RSV, respiratory syncytial virus; GBS, group B Streptococcus.