TEDDY Identifies Type 1 Diabetes Risk Factor
The Environmental Determinants of Diabetes in the Young or TEDDY is the largest study of its kind measuring new-borns with an increased risk of Type 1 Diabetes (T1D). The study published in Nature Medicine has uncovered an association between a genetic variant of a pancreatic cell surface-receptor and long-term viral infections.
Type 1 diabetes is an autoimmune disease that leads to the destruction of pancreatic islet β cells, resulting in a lack of insulin production. 400,000 people in the UK have T1D, and of those nearly 30,000 are children. Triggers of the condition are unconfirmed however genetic variants along with viral infections have been cited by many.
To identify potentially implicated viruses, the researchers used metagenomic sequencing on stool samples of 383 children with islet autoimmunity – widely seen as a precursor to T1D – and a further 112 with T1D. As a longitudinal study thousands of samples were collected (an admittedly unenviable task) that provided a comprehensive picture of the ‘virome.’ Virome refers to the collection of DNA and RNA molecules that represent the viral community in an organism.
Analysis of the virome identified the presence of enterovirus B (EV-B) and a lower proportion of human mastadenovirus than healthy controls. Long ongoing EV-B infections were associated with an increased risk of developing T1 but not short frequent bouts. Prolonged ‘shedding’ of genetic material is a hallmark of an ongoing viral infection.
In addition, the study identified a genetic variant known a single nucleotide polymorphism (SNP), that correlated with EV-B infections and islet autoimmunity risk. The SNP is located in the CXADR gene, a cell receptor gene that is highly expressed on pancreatic β cells. These cell receptors are the method of entry for a particular EV-B virus – coxsackievirus B (CVB) – providing a link between a genetic variant, increased susceptibility to viral infection, and T1D.
Prolonged shedding may be used as a biomarker for identifying those at risk of developing T1D, or even an altered virome. Although vaccines are in development, more work is required to explore the complex interactions between viruses and our cells, and why long-term infections can lead to permanent immunological damage.