Autoantibodies to αS1-Casein Are Induced by Breast-Feeding

BACKGROUND: The 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. METHODS: 62 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. RESULTS: IgG-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. CONCLUSION: We postulate that human CSN1S1 is an autoantigen. The antigenicity is orally determined, caused by breast-feeding, and sustained into adulthood

Investigating the non-specific effects of BCG vaccination on the innate immune system in Ugandan neonates: study protocol for a randomised controlled trial.

BACKGROUND: The potential for Bacillus Calmette-Guérin (BCG) vaccination to protect infants against non-mycobacterial disease has been suggested by a randomised controlled trial conducted in low birth-weight infants in West Africa. Trials to confirm these findings in healthy term infants, and in a non-West African setting, have not yet been carried out. In addition, a biological mechanism to explain such heterologous effects of BCG in the neonatal period has not been confirmed. This trial aims to address these issues by evaluating whether BCG non-specifically enhances the innate immune system in term Ugandan neonates, leading to increased protection from a variety of infectious diseases. METHODS: This trial will be an investigator-blinded, randomised controlled trial of 560 Ugandan neonates, comparing those receiving BCG at birth with those receiving BCG at 6 weeks of age. This design allows comparison of outcomes between BCG-vaccinated and -naïve infants until 6 weeks of age, and between early and delayed BCG-vaccinated infants from 6 weeks of age onwards. The primary outcomes of the study will be a panel of innate immune parameters. Secondary outcomes will include clinical illness measures. DISCUSSION: Investigation of the possible broadly protective effects of neonatal BCG immunisation, and the optimal vaccination timing to produce these effects, could have profound implications for public healthcare policy. Evidence of protection against heterologous pathogens would underscore the importance of prioritising BCG administration in a timely manner for all infants, provide advocacy against the termination of BCG's use and support novel anti-tuberculous vaccine strategies that would safeguard such beneficial effects. TRIAL REGISTRATION: ISRCTN59683017 : registration date: 15 January 2014