ABSTRACT
Insulin autoantibodies (IAA) can appear in children within months of introducing solid foods to the diet and before clinical type 1 diabetes. The aim of this study was to determine whether infant dietary antigens could be immunizing agents of IAA. To this end, IAA binding to [(125) I]insulin was competed with food preparations and extracts of foods encountered in the infant diet (milk formulas, bovine milk, wheat flour, fowl meal). Bovine milk powder extracts inhibited IAA-positive samples from six of 53 children (age 0·3-14·0 years) participating in German prospective cohorts. Inhibition in these sera ranged from 23 to 100%. Competition was abolished when hydrolyzed milk powder was used. Competition with protein components of bovine milk found that two of the six milk-reactive sera were inhibited strongly by alpha- and beta-casein; none were inhibited by the milk proteins bovine serum albumin or lactoglobulins. The two casein-reactive sera had high affinity to alpha-casein (1·7×10(9) ; 3·1×10(9) l/mol), and lesser affinity to beta-casein (4·0×10(8) ; 7·0×10(7) l/mol) and insulin (2·6×10(8) ; 1·6×10(8) l/mol). No children with milk-reactive IAA developed autoantibodies to other islet autoantigens or diabetes (median follow-up 9·8 years). These results suggest that autoimmunity to insulin can occur infrequently via cross-reactivity to food proteins, but this form of IAA immunization does not appear to be associated with progression to diabetes.
Subject(s)
Autoantibodies/immunology , Caseins/immunology , Insulin Antibodies/immunology , Insulin/immunology , Adolescent , Animals , Autoantibodies/metabolism , Binding, Competitive , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Caseins/metabolism , Caseins/pharmacology , Cattle , Cell Proliferation/drug effects , Child , Child, Preschool , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/metabolism , Flow Cytometry , Humans , Infant , Infant Food , Insulin/metabolism , Insulin/pharmacology , Insulin Antibodies/metabolism , Iodine Radioisotopes , Milk Proteins/immunology , Milk Proteins/metabolism , Milk Proteins/pharmacology , Protein Binding , Serum Albumin, BovineABSTRACT
Previous studies of experimental allergic encephalomyelitis (EAE) in the LER rat have suggested that amino acid differences present in the LER TCR V beta 8.2 chain may be associated with disease resistance. We report here that LEW rats bred to express a V beta 8.2 gene from DA rats, identical to that found in LER, are susceptible to EAE induction. Furthermore, T cells infiltrating the spinal cord of diseased animals primarily utilized V beta 8.2 and the associated AspSer CDR3 motif, typical of TCR V beta 8.2 chains expressed by pathogenic, anti-MBP responsive T cells in the LEW rat.
