An unprecedented discovery paves the way for the treatment of diabetes

British researchers at the University of Exeter discovered a unique genetic mutation in two brothers with type 1 diabetes that had never been seen in any human, paving the way towards new treatment options for the disease.

The mutation is found in the gene for the programmed cell death 1 protein (PD-L1 plays an important role in regulating the immune system), and may be responsible for the autoimmune form of diabetes that children develop at a very young age.

Molecular geneticist Matthew Johnson, from the University of Exeter in the UK, said: “The two brothers provide us with a unique and very important opportunity to investigate what happens when this gene is inactivated in humans.”

Type 1 diabetes is known as “autoimmune diabetes” because of the way the immune system attacks pancreatic beta cells, stopping normal insulin production. Patients have to inject insulin regularly to control blood sugar levels.

The two brothers, who were 10 and 11 years old at the time of the study, developed diabetes in the first weeks of their lives. A careful analysis of the immune cells confirmed that a unique genetic mutation prevented the PD-L1 protein from working properly.

Since PD-L1 and its receptor PD-1 combine as a kind of safety mechanism to keep the immune system in check, and cancer treatments that block PD-L1 functions can also lead to the development of diabetes, PD-L1 appears to be important in stopping the onset of type 1 diabetes. the first.

“We think that PD-L2, another ligand of PD-1 (mutation), may act as a backup system when PD-L1 is not available,” says physician-scientist Masato Ogishi, from Rockefeller University in New York. 

The researchers said that PL-D1 protein is necessary to prevent type 1 diabetes, but it is not necessary to keep many other immune system functions working as usual.

The clues provided by the genetic mutation, as well as the link between cancer treatment and diabetes, could help open new ways to treat the onset of type 1 diabetes (if researchers can figure out how PD-L1 prevents it, and how PD-L2 acts as a backup).

Immunologist Timothy Tree, from King's College London, says: "This discovery increases our knowledge of how autoimmune forms of diabetes develop. It opens a new potential target for treatments that could prevent diabetes in the future."

The research was published in the Journal of Experimental Medicine.