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. 2013 Oct;62(10):3636-40.
doi: 10.2337/db13-0300. Epub 2013 Jul 8.

Patterns of β-cell autoantibody appearance and genetic associations during the first years of life

Jorma Ilonen  1 , Anna Hammais, Antti-Pekka Laine, Johanna Lempainen, Outi Vaarala, Riitta Veijola, Olli Simell, Mikael Knip
Affiliations

Patterns of β-cell autoantibody appearance and genetic associations during the first years of life

Jorma Ilonen et al. Diabetes. 2013 Oct.

Abstract

We analyzed demographic and genetic differences between children with various diabetes-associated autoantibodies reflecting the autoimmune process. In a prospective birth cohort comprising children with HLA-conferred susceptibility to type 1 diabetes (T1D), the pattern of autoantibody appearance was analyzed in 520 children with advanced β-cell autoimmunity associated with high risk for disease. In 315 cases, a single biochemical autoantibody could be identified in the first positive sample as insulin (insulin autoantibody [IAA]) in 180, as GAD (GAD antibody [GADA]) in 107, and as IA-2 antigen (IA-2 antibody [IA-2A]) in 28. The age at seroconversion differed significantly between the three groups (P = 0.003). IAA as the first autoantibody showed a peak time of appearance during the second year of life, whereas GADA as the first autoantibody peaked later, between 3 and 5 years of age. The risk-associated insulin gene rs689 A/A genotypes were more frequent in children with IAA as the first autoantibody compared with the other children (P = 0.002). The primary autoantigen in the development of β-cell autoimmunity and T1D seems to strongly correlate with age and genetic factors, indicating heterogeneity in the initiation of the disease process.

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Figures

FIG. 1.
FIG. 1.
Progression to clinical T1D among children with advanced autoimmunity when divided according to the first biochemical autoantibody to appear (IAA, dashed line; GADA, solid line; and IA-2A, dotted line). The follow-up started when the first biochemical autoantibody appeared. AAB, autoantibody.
FIG. 2.
FIG. 2.
The age distribution for the appearance of the first autoantibody in the group of children with advanced β-cell autoimmunity (left panels) compared with the age distribution for the secondary autoantibodies appearing after the first autoantibody (right panels). The clear differences seen in the first autoantibody are masked by secondary autoantibodies if combined.
See this image and copyright information in PMC

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