High-Affinity Autoantibodies Predicts Progression to Diabetes

Children with high-affinity insulin autoantibodies (IAAs) are more likely than those with lower-affinity IAAs to develop type 1 diabetes. Virtually all children who develop diabetes have IAAs, but not all children who have IAAs become diabetic. To investigate why this occurs, Dr. Ezio Bonifacio, from the Diabetes Research Institute in Munich, Germany, and colleagues assessed whether autoantibody maturity, as reflected by affinity, predicted which children with IAAs would develop diabetes.

The researchers assessed IAA affinity in blood samples obtained from 56 children followed in the BABYDIAB study. High-affinity IAAs were associated with young age of IAA appearance, HLA DRB1*04, and progression to diabetes.

Multiple antibody-positive children had IAA affinities that were about 100-times higher than those of single antibody-positive children or those who became autoantibody negative. All high-affinity antibodies were reactive with proinsulin, whereas lower-affinity antibodies were not.

"This is the first study to examine islet autoantibody affinity over time and, in particular, from a very young age close to the development of islet autoimmunity," the authors note.

"The findings indicate that the measurement of IAA affinity in children who are only IAA-positive will be helpful in distinguishing who is more likely to develop multiple islet autoantibodies and to progress to type 1 diabetes," the researchers conclude. J Clin Invest 2004;114:589-597.

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