British researchers at the University of Exeter have discovered a unique genetic mutation – identified in two children, siblings – that has never been seen in humans before and that opens the way to new treatment options for type 1 diabetes. News.ro.
The mutation is in the gene for a protein called PD-L1 (programmed cell death ligand 1), which acts as a kind of “brake” to keep the body’s immune responses under control.
The new study explains how the protein may be responsible for the autoimmune form of diabetes that children developed at a very young age.
“We’ve looked around the globe, looking at all the large-scale data sets we know of, and we haven’t been able to find another family,” says molecular geneticist Matthew Johnson, from the University of Exeter.
“Therefore, these siblings give us a unique and incredibly important opportunity to investigate what happens when this gene is turned off in humans.”
The genetic mutation helps the immune system to function normally
Type 1 diabetes is also known as autoimmune diabetes because of the way the body’s built-in immune system attacks the pancreatic beta cells, stopping normal insulin production.
People with this condition must inject insulin regularly to manage their blood sugar levels.
The two brothers, aged 10 and 11 at the time of the study, developed diabetes in the first weeks of life.
A closer look at the immune cells present in the two children confirmed that their unique genetic mutation prevented the PD-L1 protein from working properly.
Since PD-L1 and its receptor PD-1 combine as a sort of safety mechanism to keep the immune system in check, and cancer treatments that block PD-L1 functions can also lead to diabetes, it appears that PD-L1 protein has a key role in preventing type 1 diabetes.
However, in a surprising twist, it turned out that the immune systems of the two young brothers were functioning quite normally, even without the regulation of the immune system that PD-L1 and PD-1 normally provide.
“We believe that PD-L2, another ligand of PD-1, although less studied than PD-L1, could serve as a backup system when PD-L1 is not available,” says researcher Masato Ogishi of the University Rockefeller of New York.
A key conclusion reached by the researchers is that the PD-L1 protein is essential for the prevention of type 1 diabetes, but not as important for maintaining many other functions of the immune system.
The discovery increases knowledge about how autoimmune forms of diabetes develop
The clues provided by the discovery of this genetic mutation, plus the link between cancer treatment and diabetes, could help unlock new ways to approach the onset of type 1 diabetes – if researchers can learn how PD-L1 prevents it and how PD-L2 act as a backup solution.
“Now we need to find out what is the communication between the different types of cells that is essential for preventing autoimmune diabetes,” says immunologist Timothy Tree from King’s College London in the UK.
“This discovery adds to our knowledge of how autoimmune forms of diabetes, such as type 1 diabetes, develop and points to a potential new target for treatments that could prevent diabetes in the future,” concluded the authors of this discovery.
The research was recently published in the Journal of Experimental Medicine – JEM.
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Tags: genetic mutation discovered researchers prevent diabetes
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