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.
RCT Entities:
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), bovineserum albumin, and alpha-casein and IgG antibodies to bovineinsulin (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.
Authors: R Carratù; M Secondulfo; L de Magistris; D Iafusco; A Urio; M G Carbone; G Pontoni; M Cartenì; F Prisco Journal: J Pediatr Gastroenterol Nutr Date: 1999-03 Impact factor: 2.839
Authors: J Ilonen; H Reijonen; E Herva; M Sjöroos; A Iitiä; T Lövgren; R Veijola; M Knip; H K Akerblom Journal: Diabetes Care Date: 1996-08 Impact factor: 19.112
Authors: S M Virtanen; L Räsänen; K Ylönen; A Aro; D Clayton; B Langholz; J Pitkäniemi; E Savilahti; R Lounamaa; J Tuomilehto Journal: Diabetes Date: 1993-12 Impact factor: 9.461
Authors: Mikael Knip; Suvi M Virtanen; Dorothy Becker; John Dupré; Jeffrey P Krischer; Hans K Åkerblom Journal: Am J Clin Nutr Date: 2011-06-08 Impact factor: 7.045