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Open Access Green as soon as Postprint is submitted to ZB.
IA-2 autoantibody affinity in children at risk for type 1 diabetes.
Clin. Immunol. 145, 224-229 (2012)
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
Language
english
Publication Year
2012
HGF-reported in Year
2012
ISSN (print) / ISBN
1521-6616
e-ISSN
1521-7035
Journal
Clinical Immunology
Quellenangaben
Volume: 145,
Issue: 3,
Pages: 224-229
Publisher
Elsevier
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)
Institute of Pancreatic Islet Research (IPI)
POF-Topic(s)
30201 - Metabolic Health
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-502100-001
PubMed ID
23110943
WOS ID
WOS:000311661500005
Erfassungsdatum
2012-12-31