Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Active free secretory component and secretory IgA in human milk: do maternal vaccination, allergy, infection, mode of delivery, nutrition and active lifestyle change their concentrations?

Abstract

Background

Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated.

Methods

Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA.

Results

Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors.

Conclusion

This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk.

Impact

  • Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk.

  • Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion.

  • Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: The secretion of secretory IgA (SIgA) and free secretory component (free SC) in human milk.
Fig. 2: Vaccination during pregnancy and free secretory component in human milk.
Fig. 3: Maternal allergy and free secretoty component in human milk.
Fig. 4: Nutrition and active lifestyle on free secretory component in human milk.
Fig. 5: Specificity of ELISA to detect free secretory component and secretory IgA.

References

  1. 1.

    Isobe, Y., Chen, S. T., Nakane, P. K. & Brown, W. R. Studies on translocation of immunoglobulins across intestinal epithelium. Acta Histochem. Cytoch. 10, 161–171 (1977).

    CAS  Google Scholar 

  2. 2.

    Weicker, J. & Underdown, B. J. A study of the association of human secretory component with IgA and IgM proteins. J. Immunol. 114, 1337–1344 (1975).

    CAS  PubMed  Google Scholar 

  3. 3.

    Watson, D. Immunological functions of the mammary gland and its secretion-comparative review. Aust. J. Biol. Sci. 33, 403–422 (1980).

    CAS  PubMed  Google Scholar 

  4. 4.

    Brandtzaeg, P. et al. The B‐cell system of human mucosae and exocrine glands. Immunol. Rev. 171, 45–87 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Lindh, E. Increased resistance of immunoglobulin A dimers to proteolytic degradation after binding of secretory component. J. Immunol. 114, 284–286 (1975).

    CAS  PubMed  Google Scholar 

  6. 6.

    Berdoz, J., Blanc, C. T., Reinhardt, M., Kraehenbuhl, J. P. & Corthésy, B. In vitro comparison of the antigen-binding and stability properties of the various molecular forms of IgA antibodies assembled and produced in CHO cells. Proc. Natl. Acad. Sci. USA 96, 3029–3034 (1999).

    CAS  PubMed  Google Scholar 

  7. 7.

    Dickinson, E. C. et al. Immunoglobulin A supplementation abrogates bacterial translocation and preserves the architecture of the intestinal epithelium. Surgery 124, 284–290 (1998).

    CAS  PubMed  Google Scholar 

  8. 8.

    Mazanec, M. B., Nedrud, J. G., Kaetzel, C. S. & Lamm, M. E. A three-tiered view of the role of IgA in mucosal defense. Immunol. Today 14, 430–435 (1993).

    CAS  PubMed  Google Scholar 

  9. 9.

    Giugliano, L. G., Ribeiro, S. T. G., Vainstein, M. H. & Ulhoa, C. J. Free secretory component and lactoferrin of human milk inhibit the adhesion of enterotoxigenic Escherichia coli. J. Med. Microbiol. 42, 3–9 (1995).

    CAS  PubMed  Google Scholar 

  10. 10.

    Dallas, S. D. & Rolfe, R. D. Binding of Clostridium difficile toxin A to human milk secretory component. J. Med. Microbiol. 47, 879–888 (1998).

    CAS  PubMed  Google Scholar 

  11. 11.

    Hammerschmidt, S., Talay, S. R., Brandtzaeg, P. & Chhatwal, G. S. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol. Microbiol. 25, 1113–1124 (1997).

    CAS  PubMed  Google Scholar 

  12. 12.

    Mathias, A. & Corthésy, B. Recognition of gram-positive intestinal bacteria by hybridoma-and colostrum-derived secretory immunoglobulin A is mediated by carbohydrates. J. Biol. Chem. 286, 17239–17247 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Murthy, A. K. et al. Mannose-containing oligosaccharides of non-specific human secretory immunoglobulin A mediate inhibition of Vibrio cholerae biofilm formation. PLoS ONE 6, e16847 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Murthy, A. K., Dubose, C. N., Banas, J. A., Coalson, J. J. & Arulanandam, B. P. Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium‐induced colitis. J. Gastroenterol. Hepatol. 21, 1372–1380 (2006).

    CAS  PubMed  Google Scholar 

  15. 15.

    De Araujo, A. N. & Giugliano, L. G. Lactoferrin and free secretory component of human milk inhibit the adhesion of enteropathogenic Escherichia coli to HeLa cells. BMC Microbiol. 1, 25 (2001).

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Perrier, C., Sprenger, N. & Corthésy, B. Glycans on secretory component participate in innate protection against mucosal pathogens. J. Biol. Chem. 281, 14280–14287 (2006).

    CAS  PubMed  Google Scholar 

  17. 17.

    Royle, L. et al. Secretory IgA N-and O-glycans provide a link between the innate and adaptive immune systems. J. Biol. Chem. 278, 20140–20153 (2003).

    CAS  PubMed  Google Scholar 

  18. 18.

    Rognum, T. O., Thrane, P. S., Stoltenberg, L., Vege, Å. & Brandtzaeg, P. Development of intestinal mucosal immunity in fetal life and the first postnatal months. Pediatr. Res. 32, 145–148 (1992).

    CAS  PubMed  Google Scholar 

  19. 19.

    Jain, N. & Walker, W. A. Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis. Nat. Rev. Gastroenterol. Hepatol. 12, 14–25 (2014).

    PubMed  Google Scholar 

  20. 20.

    Demers-Mathieu, V. et al. Differences in maternal immunoglobulins within mother’s own breast milk and donor breast milk and across digestion in preterm infants. Nutrients 11, 920 (2019).

    CAS  PubMed Central  Google Scholar 

  21. 21.

    Dallas, S. & Rolfe, R. Binding of Clostridium difficile toxin A to human milk secretory component. J. Med. Microbiol. 47, 879–888 (1998).

    CAS  PubMed  Google Scholar 

  22. 22.

    Demers-Mathieu, V. et al. Antenatal influenza A-specific IgA, IgM, and IgG antibodies in mother’s own breast milk and donor breast milk, and gastric contents and stools from preterm infants. Nutrients 11, 1567 (2019).

    CAS  PubMed Central  Google Scholar 

  23. 23.

    Demers-Mathieu, V., Underwood, M. A., Beverly, R. L., Nielsen, S. D. & Dallas, D. C. Comparison of human milk immunoglobulin survival during gastric digestion between preterm and term infants. Nutrients 10, 631 (2018).

    PubMed Central  Google Scholar 

  24. 24.

    Mehta, R. & Petrova, A. Biologically active breast milk proteins in association with very preterm delivery and stage of lactation. J. Perinatol. 31, 58 (2011).

    CAS  PubMed  Google Scholar 

  25. 25.

    Breakey, A. A., Hinde, K., Valeggia, C. R., Sinofsky, A. & Ellison, P. T. Illness in breastfeeding infants relates to concentration of lactoferrin and secretory immunoglobulin A in mother’s milk. Evol. Med. Public Health 2015, 21–31 (2015).

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Hassiotou, F. et al. L. Maternal and infant infections stimulate a rapid leukocyte response in breastmilk. Clin. Transl. Immunol. 2, e3 (2013).

    CAS  Google Scholar 

  27. 27.

    Raya, B. A. et al. The induction of breast milk pertussis specific antibodies following gestational tetanus–diphtheria–acellular pertussis vaccination. Vaccine 32, 5632–5637 (2014).

    PubMed  Google Scholar 

  28. 28.

    Insel, R. A. Potential alterations in immunogenicity by combining or simultaneously administering vaccine components. Ann. N. Y. Acad. Sci. 754, 35–48 (1995).

    CAS  PubMed  Google Scholar 

  29. 29.

    Siddiqua, T. J. et al. Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh. Eur. J. Nutr. 55, 1 (2019).

    Google Scholar 

  30. 30.

    Lang, P. O. & Aspinall, R. Can we translate vitamin D immunomodulating effect on innate and adaptive immunity to vaccine response? Nutrients 7, 2044–2060 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Jafarzadeh, A. et al. The association of the vitamin D status with the persistence of anti-HBs antibody at 20 years after primary vaccination with recombinant hepatitis B vaccine in infancy. Clin. Res. Hepatol. Gastroenterol. 41, 66–74 (2017).

    CAS  PubMed  Google Scholar 

  32. 32.

    Khodayar-Pardo, P., Mira-Pascual, L., Collado, M. C. & Martinez-Costa, C. Impact of lactation stage, gestational age and mode of delivery on breast milk microbiota. J. Perinatol. 34, 599–605 (2014).

    CAS  PubMed  Google Scholar 

  33. 33.

    Perez, P. F. et al. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics 119, e724–e732 (2007).

    PubMed  Google Scholar 

  34. 34.

    Donnet-Hughes, A. et al. Potential role of the intestinal microbiota of the mother in neonatal immune education. P. Nutr. Soc. 69, 407–415 (2010).

    Google Scholar 

  35. 35.

    Wu, W. et al. Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. Mucosal Immunol. 10, 946–956 (2016).

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    LeBlanc, J. G. et al. Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb. Cell Fact. 16, 1 (2019).

    Google Scholar 

  37. 37.

    Baldassarre, M. et al. Administration of a multi-strain probiotic product to women in the perinatal period differentially affects the breast milk cytokine profile and may have beneficial effects on neonatal gastrointestinal functional symptoms. Nutrients 8, 677 (2016).

    PubMed Central  Google Scholar 

  38. 38.

    Quin, C. et al. Probiotic supplementation and associated infant gut microbiome and health: a cautionary retrospective clinical comparison. Sci. Rep. 8, 1–16 (2018).

    CAS  Google Scholar 

  39. 39.

    Kuitunen, M., Kukkonen, A. K. & Savilahti, E. Impact of maternal allergy and use of probiotics during pregnancy on breast milk cytokines and food antibodies and development of allergy in children until 5 years. Int. Arch. Allergy Immunol. 159, 162–170 (2012).

    CAS  PubMed  Google Scholar 

  40. 40.

    Böttcher, M. F., Jenmalm, M. C., Garofalo, R. P. & Björkstén, B. Cytokines in breast milk from allergic and nonallergic mothers. Pediatr. Res. 47, 157 (2000).

    PubMed  Google Scholar 

  41. 41.

    Lovelady, C. A., Hunter, C. P. & Geigerman, C. Effect of exercise on immunologic factors in breast milk. Pediatrics 111, e148–e152 (2003).

    PubMed  Google Scholar 

Download references

Acknowledgements

We thank all study participants for their valuable contributions. We also want to thank Adrianne Weir and Jennifer Medo for the recruitment of mothers and the management of milk samples. The authors disclosed receipt of the financial support from Medolac Laboratories (A Public Benefit Corporation) for the conduct of the study.

Author information

Affiliations

Authors

Contributions

V.D.-M. conceptualized and designed the study, carried out the statistical analysis, drafted the manuscript, and approved the final paper as submitted. V.D.-M. has primary responsibility for the final content. G.M., C.D., and D.M.D. carried out ELISA analyses and E.M. conceptualized the study. G.M., C.D., D.M.D., and E.M. critically revised the paper and approved the final paper as submitted.

Corresponding author

Correspondence to Veronique Demers-Mathieu.

Ethics declarations

Competing interests

The authors are employees of Medolac Laboratories (A Public Benefit Corporation).

Patient consent

Written consents to use their milk for research were obtained from those mothers.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Demers-Mathieu, V., Mathijssen, G., Dapra, C. et al. Active free secretory component and secretory IgA in human milk: do maternal vaccination, allergy, infection, mode of delivery, nutrition and active lifestyle change their concentrations?. Pediatr Res 89, 795–802 (2021). https://doi.org/10.1038/s41390-020-0966-7

Download citation

Further reading

Search

Quick links