Discovery opens door to new therapies for type 1 diabetes

Researchers at St Vincent’s Institute in Melbourne have identified a key target of the immune response that causes type 1 diabetes.

Type 1 diabetes is an incurable autoimmune disease caused by the destruction of insulin-producing beta cells in the pancreas by immune cells called T cells. A specific type of T cell, a CD4⁺ T cell, recognizes a part of the beta cell (called an antigen) as foreign, initiating the immune response. Researchers have long been searching for the identity of the antigen that drives the disease.

Earlier work from A/Prof Mannering’s group showed that CD4⁺ T cells in the pancreas of an organ donor who hadtype 1 diabetes responded to a specific part of insulin’s precursor, proinsulin, known as C-peptide.

This study, published in the journal PNAS (Proceedings of the National Academies of Sciences)this week, showed that the blood taken from the arm of people with recent onset type 1 diabetes contained T cells that recognised C-peptide. A/Prof Mannering with his PhD student Dr Michelle So and colleagues from MCRI, WEHI and the University of Melbourne,showed that C-peptide was recognised by CD4⁺ T cells from the blood of more than 60% of people with recently diagnosed type 1 diabetes, but in less than 10% of people without the disease. In addition, C-peptide was found to be presented to CD4⁺ T cells by specific cell-surface proteins already known to be associated with a high-risk of developing type 1 diabetes.

A/Prof Mannering says that this study is different from earlier ones, which looked at fragments of the C-peptide in isolation.

Our study shows that the T cells respond most robustly to the full-length C-peptide. This points to C-peptide being an important, clinically relevant target of disease-causing CD4⁺ T cells in people with type 1 diabetes. This knowledge will allow us to begin to develop preventative therapies to stop the aberrant immune response before it does irreversible damage.”

In addition, our results will allow the development of blood tests to determine whether a person is likely to get type 1 diabetes and to measure how well a therapy to stop the progression of the disease is working.”

Dr So says that someone with type 1 diabetes must constantly be aware of their blood glucose levels, which are influenced by the amount of insulin in their system, what they eat, how much they exercise, as well as other factors like stress and illness.

“While insulin injections or infusion keep a person with type 1 diabetes alive, they don’t cure the disease, or prevent long-term complications in people who are unable to keep their blood glucose within target levels. If we could curb the immune system before the insulin-producing cells are destroyed, this would represent a huge step forward.”