The study focused on two siblings who were diagnosed with a rare genetic form of autoimmune diabetes in the first weeks of life. Despite extensive testing, no known genetic mutations were found in the siblings. Through whole genome sequencing, researchers identified a mutation in the gene encoding PD-L1 in the siblings, a gene that plays a crucial role in sending a stop signal to the immune system. This mutation could be responsible for their early-onset autoimmune diabetes, as it disabled the function of PD-L1 protein, which prevents collateral damage to the body’s tissues and organs.
Collaborating researchers from the Rockefeller Institute in New York and King’s College London joined forces with the University of Exeter to study the siblings and their rare genetic mutation. The study was funded by Wellcome, The Leona M. and Harry B. Helmsley Charitable Trust, Diabetes UK, and the US National Institutes for Health. Through extensive analysis of the siblings’ immune cells, the researchers found that while PD-L1 is essential for preventing autoimmune diabetes, it is not essential for other aspects of the immune system. They theorized that PD-L2, another protein that interacts with PD-1, might serve as a backup system when PD-L1 is disabled.
The findings from this study provide new insights into the development of autoimmune diabetes, particularly type 1 diabetes. Understanding the role of PD-L1 in preventing the immune system from attacking beta cells in the pancreas could lead to new potential targets for treatments that could prevent diabetes in the future. The study also has implications for the field of cancer immunotherapy, as manipulating PD-L1 levels is already a treatment option for cancer. By revealing the effects of completely disabling PD-L1 in a person, the researchers hope to accelerate the search for new and improved drugs.
Dr. Lucy Chambers from Diabetes UK highlighted the potential impact of this discovery on the treatment of type 1 diabetes, particularly in advancing immune system-targeted treatments. Ben Williams from The Leona M. and Harry B. Helmsley Charitable Trust emphasized the importance of human genetic evidence in drug development, pointing to the compelling evidence provided by this study that supports PD-L1 as a high-priority target for treating type 1 diabetes. This research opens up new possibilities for more effective and targeted treatments for individuals with or at risk of developing type 1 diabetes.
The paper, published in the Journal of Experimental Medicine, details the research findings and the potential implications for future treatments for type 1 diabetes. The study sheds light on the role of PD-L1 in preventing autoimmune diabetes and highlights the importance of understanding the genetic and immunological factors that contribute to the development of the disease. By identifying a unique genetic mutation in two siblings and studying its effects on the immune system, researchers are hopeful that this discovery will lead to new and innovative treatments for type 1 diabetes in the future.
