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Dietary insulin as an immunogen and tolerogen.

Abstract

We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance.

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  • Authors+Show Affiliations

    ,

    Department of Viral Diseases and Immunology, Laboratory for Immunology, National Public Health Institute, Helsinki, Finland. minna.tiittanen@ktl.fi

    , , , , , , ,

    Source

    MeSH

    Animals
    Antigens
    Autoantibodies
    Cattle
    Diabetes Mellitus, Type 1
    Diet
    Humans
    Immune Tolerance
    Immunoglobulin G
    Infant
    Infant Formula
    Infant, Newborn
    Insulin
    Milk
    Milk, Human

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17014631

    Citation

    Tiittanen, Minna, et al. "Dietary Insulin as an Immunogen and Tolerogen." Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology, vol. 17, no. 7, 2006, pp. 538-43.
    Tiittanen M, Paronen J, Savilahti E, et al. Dietary insulin as an immunogen and tolerogen. Pediatr Allergy Immunol. 2006;17(7):538-43.
    Tiittanen, M., Paronen, J., Savilahti, E., Virtanen, S. M., Ilonen, J., Knip, M., ... Vaarala, O. (2006). Dietary insulin as an immunogen and tolerogen. Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology, 17(7), pp. 538-43.
    Tiittanen M, et al. Dietary Insulin as an Immunogen and Tolerogen. Pediatr Allergy Immunol. 2006;17(7):538-43. PubMed PMID: 17014631.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dietary insulin as an immunogen and tolerogen. AU - Tiittanen,Minna, AU - Paronen,Johanna, AU - Savilahti,Erkki, AU - Virtanen,Suvi M, AU - Ilonen,Jorma, AU - Knip,Mikael, AU - Akerblom,Hans K, AU - Vaarala,Outi, AU - ,, PY - 2006/10/4/pubmed PY - 2007/2/3/medline PY - 2006/10/4/entrez SP - 538 EP - 43 JF - Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology JO - Pediatr Allergy Immunol VL - 17 IS - 7 N2 - We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance. SN - 0905-6157 UR - https://www.unboundmedicine.com/medline/citation/17014631/full_citation L2 - https://doi.org/10.1111/j.1399-3038.2006.00447.x DB - PRIME DP - Unbound Medicine ER -