title: Insulin autoantibodies with high affinity to the bovine milk protein alpha casein.
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.
authors.affiliation: Diabetes Research Institute, Forschergruppe Diabetes e.V., Munich Center for Regenerative Therapies - Dresden, Dresden University of Technology, Dresden, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Adler
authors.forename: D B
authors.initials: DB
authors.lastname: Mueller
authors.forename: P
authors.initials: P
authors.lastname: Achenbach
authors.forename: S
authors.initials: S
authors.lastname: Krause
authors.forename: A-K
authors.initials: AK
authors.lastname: Heninger
authors.forename: A G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
mesh_terms: D000293:Adolescent; D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002364:Caseins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D007225:Infant Food; D007328:Insulin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007330:Insulin Antibodies / Q000276:immunology* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008894:Milk Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D012710:Serum Albumin, Bovine
chemical_list: D001323:Autoantibodies; D002364:Caseins; D007328:Insulin; D007330:Insulin Antibodies; D007457:Iodine Radioisotopes; D008894:Milk Proteins; D012710:Serum Albumin, Bovine