Researchers have identified that the way some children’s immune systems respond to viruses may contribute to the development of islet autoimmunity – an early step toward type 1 diabetes (T1D) – rather than specific viruses causing the reaction.
Viruses and T1D
We still don’t fully understand what causes T1D, but we know that people with certain genes are more likely to develop it. Yet those genes don’t work alone to initiate T1D, as environmental factors also come into play to trigger its onset.
One of these environmental triggers is infection with an enterovirus. This is a group of viruses that are extremely common and usually cause mild cold or flu-like symptoms.
How does the body defend against viruses?
Antibodies are proteins made by the immune system, and they defend against harmful cells like viruses and bacteria. Specific antibodies are made against specific viruses.
Sometimes the immune system mistakenly targets the body’s own tissues, producing autoantibodies. These are a hallmark of autoimmune diseases such as T1D, multiple sclerosis and coeliac disease.
In T1D, immune cells destroy the insulin-producing beta cells, which are found within pancreatic islets. Islet autoantibodies appear early in the development of T1D.
Analysing antibodies and autoantibodies
In the new study, published in the scientific journal Diabetes, researchers compared blood samples from children with and without islet autoantibodies. Using a broad antibody screening method, they measured immune responses to many human viruses between the two groups. They then focused specifically on enteroviruses, to identify which regions of the virus the immune system was responding to.
What did the researchers find?
The researchers found that children with islet autoantibodies responded differently to enteroviral infections, as they made antibodies that targeted specific parts of enteroviruses. The results suggest that how an individual’s immune system responds to enterovirus infections in general, rather than being infected with any specific type of enterovirus, might drive the link between enterovirus infections and T1D onset.
Differences in the response between boys and girls
When the researchers examined boys and girls separately, they found notable differences in how their immune systems respond to enteroviruses.
In the children studied, boys had higher levels of antibodies targeting a specific region of an enterovirus protein. Among very young boys, stronger responses to this region were linked to earlier appearances of autoantibodies.
These findings suggest there may be a sex-specific immune response to enteroviruses, which could influence when autoimmunity begins. Further studies are needed to understand why these differences occur and what they mean for long-term T1D risk.
A target for preventing T1D
Understanding what may contribute to T1D development is crucial for developing ways to delay or prevent the onset of T1D. This study sheds crucial light on how children at increased genetic risk for T1D respond to enteroviruses, and identifies specific viral regions that are recognised differently in those who develop islet autoimmunity.
These viral sites may serve as useful markers of T1D risk, and could help guide the development of future vaccines or disease-modifying therapies. While additional research is needed, these findings bring us a step closer to targeted approaches that may one day prevent or delay T1D.
How is Breakthrough T1D involved?
The study was a collaboration between researchers across Australia and in Finland, funded by Breakthrough T1D and other organisations. The researchers used data from the Environmental Determinants of Islet Autoimmunity (ENDIA) study. The ENDIA study collected data, including biological samples, from children in Australia who have a parent or sibling with T1D from the pregnancy until 10 years of age.
