title: IA-2 autoantibody affinity in children at risk for type 1 diabetes.
abstract: 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 (>1.0×10(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-2β. 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.
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Krause
authors.forename: Ruth
authors.initials: R
authors.lastname: Chmiel
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Marlon
authors.initials: M
authors.lastname: Scholz
authors.forename: Michael
authors.initials: M
authors.lastname: Powell
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Furmaniak
authors.forename: Bernard
authors.initials: B
authors.lastname: Rees Smith
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: Peter
authors.initials: P
authors.lastname: Achenbach
mesh_terms: D000293:Adolescent; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D011446:Prospective Studies; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; C096322:ICA512 autoantibody; C024211:islet cell antibody; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8