The prevailing belief on how type 1 diabetes (T1D) develops is that the immune system mistakenly identifies insulin-producing beta cells as foreign, leading to their destruction. A new study published in Nature Medicine has found beta cells themselves may be causing the destructive immune response that leads to T1D. This is a relatively new concept in T1D research.
The research, led by Professor Bart Roep at the Leiden University Medical Centre, concluded that a mistake in making the insulin protein when beta cells are under stress could be inducing the immune response leading to T1D.
The team, with some support from JDRF funding, took clues from cancer molecules that are targeted by the immune system after successful treatment with immunotherapy. Immunotherapy is a treatment that adapts a person’s immune system to help it fight conditions such as cancer.
They found that an error in the genetic sequence of the cancer cells targeted by the adapted immune system resulted from a misreading of a DNA sequence. The wrongly read DNA sequence, which acts as a code for building proteins, resulted in the cancerous cell making a non-functional protein. It was this protein that the immune system could target, and in doing so, could seek out and destroy cancerous cells. Based on this, Professor Roep and his team believe it is a misreading of the insulin gene itself that could be producing a non-functioning protein which in turn becomes a target for the immune system. The team claims that this error in the insulin gene is made when beta cells are stressed. We still do not know what triggers cause this stress.
The findings imply beta cells may be destroyed in T1D by a mechanism similar to responses in people who have had immunotherapy for cancer tumours, where the immune system has been trained to find and destroy dysfunctional cells. As part of this ongoing research, Professor Roep’s team will now work out how they can correct the autoimmune response against beta cells to prevent the development of T1D.
The results of the study give Professor Roep new insight for his work in developing new treatments to allow the immune system to tolerate beta cells again, as well as for research into combining immunotherapy with other T1D treatments that aim to regrow beta cells.
This research highlights the importance of funding for research into new pathways for the development of T1D and looking beyond the T1D field for answers. In Australia, the JDRF-led T1DCRN recently awarded three Innovation Award grants that will explore new directions and include experts from outside the field of T1D research. This hopes to lead to new pathways towards prevention or a cure. Read more on the Innovation Awards here.