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Bender, C.* ; Schlosser, M.* ; Christen, U.* ; Ziegler, A.-G. ; Achenbach, P.

GAD autoantibody affinity in schoolchildren from the general population.

Diabetologia 57, 1911-1918 (2014)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
AIMS/HYPOTHESIS: Subtyping GAD autoantibody (GADA) responses using affinity measurement allows the identification of GADA-positive children with a family history of type 1 diabetes who are at risk of developing diabetes. Here, we asked whether GADA affinity is a useful marker to stratify the risk of type 1 diabetes in GADA-positive schoolchildren from the general population. METHODS: GADA affinity was measured by competitive binding experiments with [(125)I]-labelled and unlabelled human 65 kDa isoform of GAD (GAD65) in sera from 97 GADA-positive children identified in the Karlsburg Type 1 Diabetes Risk Study of a general schoolchild population in north-eastern Germany. GADA epitope specificity was determined using radiobinding assays with [(35)S]-labelled GAD65/67 kDa isoform of GAD (GAD67) chimeric proteins. RESULTS: GADA affinity was high, ≥10(10) l/mol, in 33 of 35 multiple islet autoantibody-positive children. In contrast, the affinity ranged widely among 62 single GADA-positive children (median 3.1 × 10(9) l/mol; range 5.6 × 10(6) to >4.0 × 10(11) l/mol; p < 0.0001). High-affinity GADA were associated with HLA-DRB1*03 (p = 0.02) and predominantly directed against the C-terminal and/or middle part of the GAD65 protein. At follow-up, the affinity remained relatively constant. Five of the single GADA-positive children developed additional islet autoantibodies and had high-affinity GADA. Twenty-six children progressed to type 1 diabetes; among them, 23 had GADA affinities of ≥10(10) l/mol before disease onset. CONCLUSIONS/INTERPRETATION: Schoolchildren from the general population may develop heterogeneous GADA responses, and a high affinity can identify those GADA-positive children who are more likely to progress to type 1 diabetes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Affinity ; Gad Autoantibodies ; General Population ; Schoolchildren ; Type 1 Diabetes Risk; Type-1 Diabetes Risk; Antibody Standardization Program; Genetic Susceptibility; Zinc Transporter-8; Immune-responses; Young-children; Relatives; Disease; Pathogenesis; Progression
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Zeitschrift Diabetologia
Quellenangaben Band: 57, Heft: 9, Seiten: 1911-1918 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin ; Heidelberg [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research (IDF)
German Center for Diabetes Reseach (DZD)