Autoantibodies to αS1-Casein Are Induced by Breast-Feeding

Klaudia Petermann,Ellen Bleck,Matthias Schneider,Joachim Jose,Ruth Maas,Thorsten Saenger,Stefan Vordenbäumen,Achim Braukmann,Niyaz Ahmed

doi:10.1371/journal.pone.0032716

Klaudia Petermann, Ellen Bleck + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0032716

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Abstract

BackgroundThe generation of antibodies is impaired in newborns due to an immature immune system and reduced exposure to pathogens due to maternally derived antibodies and placental functions. During nursing, the immune system of newborns is challenged with multiple milk-derived proteins. Amongst them, caseins are the main constituent. In particular, human αS1-casein (CSN1S1) was recently shown to possess immunomodulatory properties. We were thus interested to determine if auto-antibodies to CSN1S1 are induced by breast-feeding and may be sustained into adulthood.Methods62 sera of healthy adult individuals who were (n = 37) or were not (n = 25) breast-fed against human CSN1S1 were investigated by a new SD (surface display)-ELISA. For cross-checking, these sera were tested for anti Epstein-Barr virus (EBV) antibodies by a commercial ELISA.ResultsIgG-antibodies were predominantly detected in individuals who had been nursed. At a cut-off value of 0.4, the SD-ELISA identified individuals with a history of having been breast-fed with a sensitivity of 80% and a specificity of 92%. Under these conditions, 35 out of 37 sera from healthy donors, who where breast-fed, reacted positively but only 5 sera of the 25 donors who were not breast-fed. The duration of breast-feeding was of no consequence to the antibody reaction as some healthy donors were only short term breast-fed (5 days minimum until 6 weeks maximum), but exhibited significant serum reaction against human CSN1S1 nonetheless.ConclusionWe postulate that human CSN1S1 is an autoantigen. The antigenicity is orally determined, caused by breast-feeding, and sustained into adulthood.

Highlights

The healthy human fetus is generally considered not to be significantly engaged in specific immunoglobulin production [1,2]
Materials Goat anti-human IgG conjugated with horseradish peroxidase was obtained from Beckman Coulter (Krefeld, Germany), rabbit anti-human aS1-casein (CSN1S1) was obtained from ModiQuest (Nijmegen, The Netherlands), goat anti-rabbit IgG conjugated with horseradish peroxidase was obtained from Sigma-Aldrich and goat anti-rabbit IgG conjugated with FITC was obtained from Bethly (Montgomery, USA)
Autodisplay of aS1-casein (CSN1S1) For SD-ELISA in order to detect an antibody reaction against CSN1S1, the human protein was displayed on the surface of E. coli

Summary

Introduction

The healthy human fetus is generally considered not to be significantly engaged in specific immunoglobulin production [1,2]. In the absence of foreign antigens in the fetus, self proteins may serve as an antigenic stimulus [7], creating antibodies that may be mono- or polyspecific and directed against self-tissue components [7,8] Their precise role is currently unknown, it is speculated that these autoantibodies may confer protection against foreign pathogens [8] or help to survey the state of the individual’s own cells [7,9]. Illnesses induced by these early formed autoantibodies are only rarely observed [10]. We were interested to determine if auto-antibodies to CSN1S1 are induced by breast-feeding and may be sustained into adulthood

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