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

被引:4
作者
Campo, Joseph J. [1 ]
Seppo, Antti E. [2 ]
Randall, Arlo Z. [1 ]
Pablo, Jozelyn [1 ]
Hung, Chris [1 ]
Teng, Andy [1 ]
Shandling, Adam D. [1 ]
Truong, Johnathon [1 ]
Oberai, Amit [1 ]
Miller, James [2 ]
Iqbal, Najeeha Talat [3 ]
Yori, Pablo Penataro [4 ]
Kukkonen, Anna Kaarina [5 ,6 ]
Kuitunen, Mikael [5 ,6 ]
Guterman, L. Beryl [6 ,7 ]
Morris, Shaun K. [8 ,9 ]
Pell, Lisa G. [8 ]
Al Mahmud, Abdullah [10 ]
Ramakrishan, Girija [4 ]
Heinz, Eva [11 ,12 ,13 ]
Kirkpatrick, Beth D. [12 ]
Faruque, Abu S. G. [13 ]
Haque, Rashidul [14 ,15 ,16 ]
Looney, R. John [17 ]
Kosek, Margaret N. [4 ]
Savilahti, Erkki [5 ,6 ]
Omer, Saad B. [18 ]
Roth, Daniel E. [8 ,9 ]
Petri, William A. [4 ]
Jaervinen, Kirsi M. [2 ,19 ]
机构
[1] Antigen Discovery Inc, Irvine, CA USA
[2] Univ Rochester, Sch Med, Dept Pediat, Div Allergy & Immunol, Rochester, NY USA
[3] Aga Khan Univ, Dept Paediat & Child Hlth Biol & Biomed Sci, Karachi, Pakistan
[4] Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA 22901 USA
[5] Univ Helsinki, New Childrens Hosp, Helsinki, Finland
[6] Helsinki Univ Hosp, Helsinki, Finland
[7] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA
[8] Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada
[9] Univ Toronto, Hosp Sick Children, Toronto, ON, Canada
[10] Int Ctr Diarrhoeal Dis Res, Nutr & Clin Serv Div, Dhaka, Bangladesh
[11] Univ Liverpool Liverpool Sch Trop Med, Dept Vector Biol, Liverpool, Scotland
[12] Univ Liverpool Liverpool Sch Trop Med, Dept Clin Sci, Liverpool, Scotland
[13] Wellcome Sanger Inst, Parasites & Microbes, Cambridge, England
[14] Univ Vermont, Vaccine Testing Ctr, Coll Med, Burlington, VT USA
[15] Univ Vermont, Dept Microbiol & Mol Genet, Coll Med, Burlington, VT USA
[16] Int Ctr Diarrhoeal Dis Res, Div Infect Dis, Emerging Infect & Parasitol Lab, Dhaka, Bangladesh
[17] Univ Rochester, Dept Med, Div Allergy Immunol & Rheumatol, Sch Med, Rochester, NY USA
[18] Peter ODonnell Jr Sch Publ Hlth, Dallas, TX USA
[19] Univ Rochester, Dept Microbiol & Immunol, Sch Med, Rochester, NY USA
关键词
SECRETORY IMMUNOGLOBULIN-A; SUBUNIT ROTAVIRUS VACCINE; MATERNAL ANTIBODIES; IMMUNE-RESPONSE; DOUBLE-BLIND; CAMPYLOBACTER DIARRHEA; DEVELOPING-COUNTRIES; HUMAN COLOSTRUM; INFANTS; PROTECTION;
D O I
10.1172/JCI168789
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 11066764 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).
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