Autoantibodies to αS1-Casein Are Induced by Breast-Feeding

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.

Human casein alpha s1 induces proinflammatory cytokine expression in monocytic cells by TLR4 signaling

“…It is therefore interesting to speculate that exogenous, unphosphorylated CSN1S1 in mother milk may contribute to the development of a patent immune system by triggering immune responses to potential pathogens even before major colonization of the gut by microbes including their pathogen‐associated molecular patterns such as LPS takes place. Moreover, CSN1S1 by itself gives rise to sustained specific IgG antibody production in nursed individuals . Early infantile autoantibody production in turn is speculated to confer protection to pathogens .…”

“…After separation proteins were visualized by Coomassie brilliant blue (R250) staining. CSN1S1 concentrations in the purified samples were determined by an indirect ELISA as described before . In brief, MaxiSorp ® microtiter plates (Nunc, Langenselbold, Germany) were coated with purified CSN1S1 (diluted 1:500 in PBS) for 16 h at 4°C.…”

“…However, unphosphorylated human CSN1S1 was recently shown to exert proinflammatory effects on monocytic cells, such as the potent induction of IL‐1β, GM‐CSF, IL‐6 , and to induce differentiation of monocytes toward macrophages . Furthermore, breastfed individuals display sustained CSN1S1‐IgG production into adulthood . This potentially points to a role for human CSN1S1 in connecting nutrition, innate, and adaptive immune mechanisms.…”

Naphthol AS-E Phosphate Inhibits the Activity of the Transcription Factor Myb by Blocking the Interaction with the KIX Domain of the Coactivator p300

“…The coding sequence of the KIX domain of human p300 (amino acids 556-652) was amplified by PCR with the primers 5 0 -CTCGAGG-GAATTCGGAAACAGTGGCACG-3 0 and 5 0 -GGTACCTAGTCTG-GTCCTTCGTTTTTCTTCTAGTT-3 0 , digested with XhoI and KpnI and inserted into plasmid pKP10 (33). The artificial gene encoding the KIX-AIDA-I autotransporter was transferred to the first multiple cloning site of pCOLADuet-1 (Merck Millipore).…”

Ser71 of αS1‐Casein is Phosphorylated in Breast Milk—Evidence from Targeted Mass Analysis

“…Human αS1‐casein is a low abundant member of the soluble casein fraction and an autoantigen . The protein is able to induce proinflammatory cytokine expression in monocytic cells by toll‐like receptor 4 (TLR‐4)‐signaling, it leads to in vitro differentiation of monocytes towards macrophages, and it upregulates the production of GM‐CSF via p38 MAP kinase in human monocytes .…”