Discovery of new antibody that helps detect type 1 diabetes

Researchers at the Barbara Davis Center for Childhood Diabetes and University of Colorado at Denver and Health Sciences Center's School of Medicine have discovered a fourth antibody in human blood which will help more accurately predict who is predisposed to type 1 diabetes.

The findings will be posted online the week of Oct. 15 and will be published in the Oct. 23 issue of the Proceedings of the National Academy of Sciences (PNAS).

Type 1 diabetes is an autoimmune disease that develops when the body's immune system mistakenly targets the pancreas, killing the cells that make insulin. Currently, antibodies in the blood are measured to diagnose diabetes before its onset through a simple blood test. Three antibodies are routinely measured giving a 90 percent chance of predicting disease. With the discovery of this fourth autoantibody, ZnT8, the prediction rate jumps to 96 percent.

“This is incredibly exciting for us since this new target is the first to be discovered in 10 years,” said John Hutton, PhD, research director at the Barbara Davis Center and senior author of the paper. “ZnT8 shows great value as a diagnostic tool and we believe testing for it will very quickly become routine in all of the ongoing clinical research studies. For example, this fourth autoantigen will find immediate use in identifying individuals with a family history of diabetes or a genetic predisposition to the disease for recruitment into clinical trials aimed at preventing diabetes.”

Blood from children who had been studied from birth to the onset of the disease as part of Diabetes Autoimmunity Study in the Young (DAISY) at the Barbara Davis Center were analyzed along with hundreds of newly-diagnosed patients and their unaffected relatives as controls. Seventy percent of diabetics test positive for the antibody versus less than one percent of controls.

ZnT8 was chosen from thousands of candidates using microarray analysis, a method that catalogs the level of expression of all the genes in the body on a tissue-by-tissue basis. ZnT8 stuck out as a protein that was only expressed in insulin secreting cells and associated with the mechanism of insulin release, making it a good candidate on which to follow up.

“Ultimately, we'd like to be able to prevent diabetes from occurring in the first place,” said Hutton. “It could be possible by catching it in the very early stages and then manipulating the immune system. ZnT8 itself might be part of that therapy since it has been shown in diabetes-prone mice that administering antigen as a vaccine can prevent disease, a similar approach that is currently used to counter allergies. We also hope that the same genomics-based approach will be applicable to other autoimmune diseases like multiple sclerosis and lupus.”

Hutton and his team believe they will eventually be able to define further autoantigens using the same procedures and raise the predictive value of combined autoantibody tests to the required accuracy rate of 99.7 percent. If so, they will then be able to achieve the ultimate goal of preventing diabetes through screening very young children in the general population and catching the disease in its earliest stages.

The University of Colorado at Denver and Health Sciences Center is one of three universities in the University of Colorado system. Located in Denver, on the Auraria Campus, at Ninth & Colorado Blvd. and on the Anschutz Medical Campus in Aurora, Colo., UCDHSC is Colorado's premier research university offering more than 100 degrees and programs in 12 schools and colleges and serving more than 28,000 students in Metro Denver and online.

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