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Schlosser, M.* ; Koczwara, K.* ; Kenk, H.* ; Strebelow, M.* ; Rjasanowski, I.* ; Wassmuth, R.* ; Achenbach, P.* ; Ziegler, A.-G.* ; Bonifacio, E.*

In insulin-autoantibody-positive children from the general population, antibody affinity identifies those at high and low risk.

Diabetologia 48, 1830-1832 (2005)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Aims/hypothesis: Insulin autoantibodies ( IAA) precede and predict the onset of type 1 diabetes, but not all children with IAA develop the disease. In affected families, IAA affinity can identify IAA-positive children who are more likely to progress to diabetes. The purpose of this study was to determine whether affinity is a useful marker to stratify type 1 diabetes risk in IAA-positive children from the general population. Methods: IAA affinity was determined by competitive binding to I-125-insulin with increasing concentrations of cold insulin and with cold proinsulin in sera from 46 IAA-positive children identified in the Karlsburg Type 1 Diabetes Risk Study of a Normal Schoolchild Population in north-eastern Germany. Results: IAA affinity ranged between 5 x 10(6) and 1.2 x 10(11) l/mol. IAA affinity was higher in 24 children who developed multiple islet autoantibodies or diabetes median 3.5 x 10(9) l/ mol; interquartile range [IQR] 2.1 x 10(9) to 2.1 x 10(10) l/mol) than in 22 children who did not develop multiple islet autoantibodies or diabetes ( median 1.3 x 10(8) l/ mol; IQR 3.8 x 10(7) to 7.2 x 10(8) l/ mol; p< 0.0001). Using a threshold of >= 10(9) l/ mol, 22 of the 24 children who developed multiple islet autoantibodies or diabetes were correctly identified by high-affinity IAA and 18 of 22 who did not develop multiple islet autoantibodies or diabetes were correctly identified by low-affinity IAA. IAA affinity was significantly higher in samples with proinsulin reactive IAA ( p< 0.0001). Conclusions/interpretation: IAA affinity measurement provides robust identification of IAA associated with high diabetes risk.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Antibody Affinity ; Insulin Autoantibodies ; Prediction ; Proinsulin ; Type 1 Diabetes; Diabetes-associated Autoantibodies; Schoolchildren; Autoimmunity; Appearance; Parents
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 48, Issue: 9, Pages: 1830-1832 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Diabetes and Obesity (IDO)
Institute of Pancreatic Islet Research (IPI)