In insulin-autoantibody-positive children from the general population, antibody affinity identifies those at high and low risk.
OBJECTIVE
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
IAA affinity measurement provides robust identification of IAA associated with high diabetes risk.
Schlosser
M
M
Institute of Pathophysiology, University of Greifswald, Karlsburg, Germany.
Koczwara
K
K
Kenk
H
H
Strebelow
M
M
Rjasanowski
I
I
Wassmuth
R
R
Achenbach
P
P
Ziegler
A-G
AG
Bonifacio
E
E
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007328:Insulin / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D012307:Risk Factors
D001323:Autoantibodies; D007328:Insulin