HARVARD GAZETTE ARCHIVES

Revealing the results of an eight-year research project, BWH researchers may have identified part of the puzzle underlying the cause of type 1 diabetes. They have found a single antigen (protein the body creates that leads to the development of autoimmune disease) - insulin - that appears to trigger the body to attack its own insulin-producing cells. Researchers can now use this information in clinical trials to determine if "turning off" our body's immune response to the antigen could reduce the disease's impact or eliminate its occurrence. Details of this research are being published in the May 12 issue of the journal Nature. These data will be presented at the Federation of Clinical Immunology Society conference in Boston, the world's leading forum for sharing research about human inflammatory disease. In addition, this issue of Nature will also feature a study from colleagues at the University of Colorado who report supporting results based on a mouse model of autoimmune diabetes.

According to the study's lead author BWH's David A. Hafler, Breakstone Professor of Neurology at HMS, "We are excited to be part of a growing body of evidence that points to insulin as the trigger for type 1 diabetes." Citing research contributions from BWH, including first authors Sally Kent and Yahua Chen as well as previous studies by colleagues from the Joslin Diabetes Center, Hafler stated, "We began this study by trying to identify what drives the autoimmune process in type 1 diabetes. Understanding the body's role in the development of this disease will hopefully drive the discovery of new treatments in the near future."

Type 1 diabetes occurs when autodestructive T cells infiltrate the pancreas, destroying the cells that produce insulin. To unravel the puzzle of how this autoimmune disease is triggered, researchers worked to identify and isolate the antigen involved in this specific disease. To facilitate this process, researchers cloned hundreds of T cells from pancreatic-draining lymph nodes from three subjects with type 1 diabetes and three control subjects. The cloned T cells were then tested in the lab, where researchers found that the T cells from the diabetic subjects "triggered" insulin - specifically insulin A 1-15 epitope - the potential cause of type 1 diabetes.

According to Hafler, while the scientists were surprised by how virtually all of the expanded T cells from the draining lymph nodes could recognize the single insulin antigen, they emphasize that these experiments need to be expanded to larger series of patients. According to Hafler, if insulin is driving the destruction of the cells that produce insulin, the next step involves further testing of insulin to determine if it can be manipulated to better manage the disease or prevent it altogether. Preliminary work by the University of Miami's Jay Skyler, from the NIH-sponsored Diabetes Prevention Trial, suggests that turning off immune responses to insulin may have a potentially beneficial effect on the disease.

Diabetes is a chronic disease that has no cure. Treatment for type 1 diabetes includes taking insulin shots or using an insulin pump, making wise food choices, being physically active, and for some, taking aspirin daily and controlling blood pressure and cholesterol.

This study was sponsored by the NIH's Autoimmunity Prevention Center grant.