title: 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.
authors.affiliation: Department of Viral Diseases and Immunology, Laboratory for Immunology, National Public Health Institute, Helsinki, Finland. minna.tiittanen@ktl.fi
authors.forename: Minna
authors.initials: M
authors.lastname: Tiittanen
authors.forename: Johanna
authors.initials: J
authors.lastname: Paronen
authors.forename: Erkki
authors.initials: E
authors.lastname: Savilahti
authors.forename: Suvi M
authors.initials: SM
authors.lastname: Virtanen
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Hans K
authors.initials: HK
authors.lastname: Akerblom
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D002417:Cattle; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D004032:Diet; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D041943:Infant Formula; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism*; D008892:Milk / Q000276:immunology*; D008895:Milk, Human / Q000737:chemistry*
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007074:Immunoglobulin G; D007328:Insulin