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Krause, S. ; Chmiel, R.* ; Bonifacio, E.* ; Scholz, M. ; Powell, M.* ; Furmaniak, J.* ; Smith, B.R.* ; Ziegler, A.-G. ; Achenbach, P.

IA-2 autoantibody affinity in children at risk for type 1 diabetes.

Clin. Immunol. 145, 224-229 (2012)
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Open Access Green as soon as Postprint is submitted to ZB.
Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 10(7) to 10(11) L/mol and was high (>1.0 x 10(9) L/mol) in 41(82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2 beta. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Type 1 Diabetes ; Ia-2 Autoantibodies ; Affinity ; Epitopes ; Diabetes Risk; Antibody Standardization Program ; Zinc Transporter 8 ; Epitope Specificity ; Rapid Progression ; Autoimmunity ; Relatives ; Assays ; Susceptibility ; Decarboxylase ; Prediction
Reviewing status
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Institute for Pancreatic Beta Cell Research (IPI)