Enhanced levels of cow’s milk antibodies in infancy in children who develop type 1 diabetes later in childhood
Corresponding Author
Kristiina Luopajärvi
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
Kristiina Luopajärvi, MDHospital for Children and AdolescentsUniversity of HelsinkiP.O. Box 760FIN-00029 HUSHelsinkiFinland.Tel: +358 9 471 72797;fax: +358 9 191 25229;e-mail: [email protected]Search for more papers by this authorErkki Savilahti
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Search for more papers by this authorSuvi M Virtanen
Tampere School of Public Health, University of Tampere, Tampere, Finland
Research Unit, Tampere University Hospital, Tampere, Finland
Department of Epidemiology and Health Promotion, Nutrition Unit, National Public Health Institute, Helsinki, Finland
Search for more papers by this authorJorma Ilonen
Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland
Immunogenetics Laboratory, University of Turku, Turku, Finland
Search for more papers by this authorMikael Knip
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Department of Pediatrics, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorHans K Åkerblom
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Search for more papers by this authorOuti Vaarala
Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
Search for more papers by this authorCorresponding Author
Kristiina Luopajärvi
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
Kristiina Luopajärvi, MDHospital for Children and AdolescentsUniversity of HelsinkiP.O. Box 760FIN-00029 HUSHelsinkiFinland.Tel: +358 9 471 72797;fax: +358 9 191 25229;e-mail: [email protected]Search for more papers by this authorErkki Savilahti
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Search for more papers by this authorSuvi M Virtanen
Tampere School of Public Health, University of Tampere, Tampere, Finland
Research Unit, Tampere University Hospital, Tampere, Finland
Department of Epidemiology and Health Promotion, Nutrition Unit, National Public Health Institute, Helsinki, Finland
Search for more papers by this authorJorma Ilonen
Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland
Immunogenetics Laboratory, University of Turku, Turku, Finland
Search for more papers by this authorMikael Knip
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Department of Pediatrics, Tampere University Hospital, Tampere, Finland
Search for more papers by this authorHans K Åkerblom
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Search for more papers by this authorOuti Vaarala
Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
Search for more papers by this authorAbstract
Background: Early exposure to cow’s milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D).
Objective: We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D.
Subjects and methods: We studied a subgroup of 94 children randomized to be weaned to a CM-based infant formula in the trial to reduce insulin-dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen-conferred T1D susceptibility and had an affected first-degree relative. After 7 years of follow-up, 8 subjects had progressed to T1D, 15 had at least one disease-associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta-lactoglobulin (BLG), bovine serum albumin, and alpha-casein and IgG antibodies to bovine insulin (BI) were measured with enzyme-linked immunosorbent assays from sequential samples.
Results: The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody-positive subjects than in autoantibody-negative subjects at 18 months of age (p = 0.022).
Conclusion: An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D.
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