Metabolic Biomarkers for Fibromyalgia: Administrative Supplement

点击翻译按钮获取中文摘要

Project Summary Fibromyalgia (FM) is a complex condition characterized by widespread pain - often induced by activity; fatigue; cognitive and sleep dysfunction. Activity-induced pain and fatigue in particular are significant barriers to participation in an effective exercise program and daily activities. Accordingly, improved understanding of the underlying mechanisms associated with symptomology could lead to novel approaches for effective management. This supplement will provide resources to perform preliminary analyses to investigate potential immune-related mechanisms of FM and their relationship to symptomology, particularly activity-induced pain. It has become clear that the immune system plays a key role in FM, with alterations related to clinical symptoms and activity-induced pain. However, prior studies have been equivocal in identifying specific immune cell types responsible for changes in inflammatory markers, specifically circulating cytokines, often with mixed results across studies. Further, immune cells do not work in isolation; the metabolic environment can alter immune cell phenotype, immune cells may alter the metabolic environment, and cross-talk between immune cells can occur. At the same time, epigenetic dysregulation of immune cells directly influences differentiation of immune cell phenotypes and subsets. In fact, altered DNA methylation patterns have been observed with FM; however, it is unclear which distinct cell types are involved. The primary goal of this proposal is to assess immune function using multiple assays in a single cohort of adults with FM relative to matched controls to generate pilot data for a future submission. We hypothesize that alterations in the immune system including phenotype of immune cells, evoked-release of IL-1β, and altered DNA methylation in monocytes, will occur in those with FM vs matched controls, and that these changes will relate to the clinical phenotypes of pain and fatigue. We further propose that the changes in cytokines will directly relate to the metabolome already collected in this project. This study will achieve the primary goal via two specific aims: Aim 1: Characterize the immune system using multiple techniques in FM and matched controls: 1) phenotype and quantification of monocytes, T-cells, B-cells and natural killer cells using spectral flow cytometry, 2) muscle metabolite-evoked release from monocytes, and 3) DNA methylation pattern and epigenetic age of monocytes; Aim 2: Determine the relationship of immune system and DNA methylation changes to the clinical phenotype and metabolome profiles in individuals with FM compared to matched controls. Our primary aim will focus on activity-induced pain, with secondary aims examining relationship with other symptoms, including fatigue. This research will provide new insights into underlying immune cell mechanisms in FM. These novel studies have the potential to identify diagnostic, and potentially therapeutic, FM biomarkers associated with immune cell function. The multi- institutional and multidisciplinary study team has the necessary expertise in clinical and translational science, immune function, and epigenetics to efficiently leverage data collected for the parent grant.