title: Significance of cow's milk protein antibodies as risk factor for childhood IDDM: interactions with dietary cow's milk intake and HLA-DQB1 genotype. Childhood Diabetes in Finland Study Group.
abstract: Dietary factors are suspected to play an aetiological role in the development of insulin-dependent diabetes mellitus (IDDM). We analysed cow's milk formula, betalactoglobulin, and bovine serum albumin antibodies by an enzyme-linked immunoassay in unselected children with newly diagnosed IDDM and in their non-diabetic siblings and inquired about infant feeding practices by questionnaire. Among 410 diabetic sibling pairs matched for age and sex, by logistic regression analysis - including overall duration of breast-feeding, age at introduction of dairy products, recent consumption of cow's milk and HLA-DQB1 genotype ("high/moderate" vs "low/decreased" risk of IDDM) - bovine serum albumin IgG antibody levels (OR 2.12, 95% CI 1.25-3.57) and genetic risk (OR 3.81, 95% CI 2.43-5.17) were positively associated with IDDM; cow's milk formula IgM antibodies were inversely associated with the risk of IDDM (OR 0.50, 95% CI 0.29-0.87). Of the diabetic sibling pairs, 42 were identical for HLA-DQB1 alleles associated with IDDM risk or protection (DQB1*0201, *0301, *0302 and *0602/03). In these 42 pairs, children with IDDM had higher median levels of bovine serum albumin IgG, of betalactoglobulin IgG, and of cow's milk formula IgG and IgA antibodies than the non-diabetic siblings (p < 0.05). In conclusion, children with IDDM have higher levels of cow's milk protein antibodies than their HLA-DQB1-matched sibling controls, and these high levels of antibodies are independent risk markers for IDDM.
authors.affiliation: Children's Hospital, University of Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Saukkonen
authors.forename: S M
authors.initials: SM
authors.lastname: Virtanen
authors.forename: M
authors.initials: M
authors.lastname: Karppinen
authors.forename: H
authors.initials: H
authors.lastname: Reijonen
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
authors.forename: L
authors.initials: L
authors.lastname: Räsänen
authors.forename: H K
authors.initials: HK
authors.lastname: Akerblom
authors.forename: E
authors.initials: E
authors.lastname: Savilahti
mesh_terms: D000818:Animals; D000917:Antibody Formation; D002417:Cattle; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007225:Infant Food; D007768:Lactalbumin / Q000276:immunology*; D008892:Milk / Q000009:adverse effects* / Q000276:immunology; D008894:Milk Proteins / Q000009:adverse effects* / Q000276:immunology; D009679:Nuclear Family; D012044:Regression Analysis; D012307:Risk Factors; D012710:Serum Albumin, Bovine / Q000276:immunology
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008894:Milk Proteins; D012710:Serum Albumin, Bovine; D007768:Lactalbumin