JDRF scientists and their colleagues recently published the key insights from a JDRF-organized workshop with leading experts who met to discuss a potential basic disease mechanism in T1D. JDRF’s unique network of scientific collaborators enables JDRF to bring together the best minds from around the world to tackle the most challenging T1D research problems. In this case, it was to define new programs to help understand why the immune system becomes broken in T1D.
In T1D and other autoimmune diseases, the body mistakenly mounts an immune response to normal or native body components, such as insulin, as opposed to only attacking foreign substances like bacteria or viruses. Normally, a person’s immune system learns to correctly distinguish between native and foreign materials. Correctly distinguishing native components is known as immune tolerance – the normal immune system learns to “tolerate” the presence of native components like our own proteins.
The mechanisms by which immune tolerance becomes broken in T1D are complex and not very well understood. One possibility, which this workshop explored, is that alterations in the structure of native components (such as proteins) might play a role. These alterations to native proteins may happen in several ways, such as the attachment of different molecules, changes to the protein’s structure, or connecting proteins in different ways. We know that a similar process occurs in other autoimmune diseases, such as celiac disease and rheumatoid arthritis, where the immune process trigger is believed to be a result of one of these alterations. So it’s possible that a similar process might trigger T1D.
So how might these native compounds that have been modified be involved in breaking immune tolerance? One possible explanation is that, after undergoing these modifications, the altered components look different to the immune system than the unmodified or normal components. The immune system then recognizes the modified protein as foreign and mistakenly mounts an immune response to similar native components.
The recent workshop and resulting publication were a first step in exploring how this process may play a role in the development of T1D. To follow up, JDRF funded a number of proposals to prove or disprove the workshop-developed theories about these key alterations in T1D. If they are found to be important in T1D, as suspected, we may be able to use them as markers of disease progression or target them with a vaccination strategy to induce immune tolerance. We also need to explore whether people at different life stages and different stages of T1D (such as children and adults, or newly diagnosed individuals) may react to different altered native components. If so, intervening in the immune process to prevent T1D may require a number of different approaches.