Immune-Genetic Biomarkers of Risk and Resiliency for GWI
Abstract
This proposal addresses the following GWIRP overarching challenge: Determinants: Identify and validate determinants of GWI via genetic and epigenetic studies. Gulf War (GW) Veterans continue to report chronic health symptoms following their return from the war including joint and muscle pain, sleepiness, problems with thinking, skin rash, and gastrointestinal problems. However, the physical cause for this chronic illness has remained a mystery. This has made identifying useful supportive care treatment strategies very difficult. New advances in the study of brain and immune system communication may provide important new clues to the physical cause of Gulf War Illness (GWI) that could lead to specific avenues of targeted supportive care treatment strategies to improve the daily symptoms that impact on the Veterans’ quality of life. Only recently has the importance of brain-immune system cross-talk been recognized and appears to work through the immune cells of the brain, which are able to detect foreign invaders in the brain such as bacteria that can cause infection. This type of response can be quite helpful when we have an infection and our body needs rest to fight it off and get better. However, there appears to be times when this system gets caught in a loop of continuous activation, resulting in long-lasting or chronic sickness behaviors, and GWI is one of these. What is less clear is why only some GW neurotoxicant-exposed Veterans have GWI while others do not. We have recently identified differences in genetic make-up in GW Veterans with GWI compared to GW Veterans without GWI and that there is a complex interaction between genetics and deployment-related exposures. The proposed study will validate these preliminary findings to identify specific genetic and epigenetic markers of GWI and how these markers together with deployment-related exposures cause chronic sickness. We will use blood and DNA samples taken from 300 Veterans with GWI and 200 Veterans without GWI for detecting these specific markers. We will also be collecting demographic, GW-related deployment exposures to neurotoxicants, and clinical data from each Veteran that together with the marker information will allow us to determine any interactions between markers and this data. The risk for Veterans participating in this study will be minimal and equal to the risks of having a blood sample collected, for example, bruising where the blood sample was collected for a short time. Observations from these studies could identify particular markers in Veterans with GWI that can be then be used to diagnose GWI for the first time. They will also provide further insights about the complex interactions between sickness behavior responses, deployment-related exposures and risk of developing of GWI. This knowledge will be very important for future supportive care treatment of GWI symptoms that target specific responses using a personalized or precision medicine approach to reduce morbidity and mortality. To improve care for current Veterans with GWI, we first have to have markers to diagnose GWI, which this study will achieve within the 3-year study period. Based on these results, our next studies will then focus on targeting already approved medications that can be repurposed for improving the supportive care medicine of GWI symptoms. In summary, this study will increase our knowledge about specific markers linked to GWI and will answer key questions of why some GW Veterans developed GWI while others did not. This knowledge will be applied clinically as a diagnostic test for GWI and will be the first step in identifying novel supportive care treatment strategies in the future in Veterans with GWI to reduce morbidity and mortality.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210720
Entities
People
- Janet K Coller
Organizations
- United States Army
- University of Adelaide