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. 2005 Sep;48(9):1830-2.
doi: 10.1007/s00125-005-1864-6. Epub 2005 Jul 12.

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

M Schlosser  1 , K Koczwara, H Kenk, M Strebelow, I Rjasanowski, R Wassmuth, P Achenbach, A-G Ziegler, E Bonifacio
Affiliations

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

M Schlosser et al. Diabetologia. 2005 Sep.

Abstract

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 125I-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] 2.1x10(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 > or = 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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