Plasma Small Extracellular RNA as a Biomarker of Autoimmune Flairs and Beta Cell Death in Type 1 Diabetes Using Frequent Prospective Peri-Onset Sampling
Abstract
Type 1 diabetes is a disease of children and young adults. It is not rare, and more than 1 in 300 young people will be affected. While it does run in families, 90% of new cases occur in a child without a close relative with the disease. Those with type 1 diabetes need insulin shots in order to stay alive, usually several shots per day. We know that autoimmunity causes type 1 diabetes. This is when the body’s immune system gets confused and attacks its own body, in this case, specifically the insulin producing beta cells in the many small islets of Langerhans in the pancreas. Scientists and doctors believe that a key to being able to prevent type 1 diabetes is to understand just when the immune system is actively attacking the pancreas. We are not able to do this now, and so immunology medicines that might be applied to prevent the progression to diabetes cannot be applied effectively. The pancreas lies deep in the abdomen, and biopsying it is very dangerous, so this cannot be done. Because the small islets are found throughout the pancreas, it is also not possible to use CAT or MRI scans to see them. All we can do in people is sample the blood to see if there are signs that the type 1 diabetes process has been active in recent years. However, these biomarkers cannot tell exactly how active the process is. The biomarkers we have now include genetic markers that identify certain children to be at much more risk than others, so we can screen kids at birth and follow those at the highest risk. We also can detect when the body is making antibodies against one or more of several different proteins found in the pancreatic beta cells, which tells us that the process is happening. In those with more than one of these such “islet antibodies,” we know that their risk of future diabetes is very high, approaching 90%. However, we don’t know if they will get diabetes next week or in 15 years. Also, we don’t know if the process that causes diabetes is active or whether it is dormant for the time being. And we can’t apply immunology medicines if we do not know about the current activity of the process. Can you imagine if you or your child had these antibody markers and was highly likely to get type 1 diabetes in the future, but you don’t know when and you cannot do anything about it? This is a huge medical challenge. To fix this problem, researchers have been trying to find markers in the blood that can tell if the autoimmune type 1 diabetes process is active and if diabetes is coming soon, and at what point an immunotherapy might slow or stop the disease. So far, they have not been successful. In this application, we propose to use a better approach to try to find biomarkers of type 1 diabetes activity. We have followed kids with multiple islet antibodies and sampled them once every month to get a set of blood samples. This is more frequent in time than any other study we know of. In this way, we hope not to miss the diabetes biomarkers, since they may go up and down quickly as the disease flares and then calms down. We propose to investigate an exciting new type of biological molecule, small RNAs, which are causing more and more excitement among investigators because of all the things they do and because, in addition to inside your body’s cells, they also are released by cells into the bloodstream where they can give information on the status of the cells they came from, cells in many different tissues in the body. We will identify these small RNA using a highly improved approach we have been working on for several years and that we believe we are experts at. It involves getting nucleic acid sequence on the molecules so we can trace them back to the islet tissue and immune cells in and around the pancreas. We feel that our frequent blood samples from kids and our approach to identify the RNA biomarkers are both unusually innovative, and if anybody can find a useful islet RNA signal in the bloodstream,
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810267
Entities
People
- William Hagopian
Organizations
- Pacific Northwest Diabetes Research Institute
- United States Army