Metabolic Biomarkers for Fibromyalgia: Administrative Supplement

项目摘要 纤维肌痛(FM)是一种复杂的疾病，其特征是广泛的疼痛--通常是由活动引起的； 认知和睡眠障碍。尤其是运动引起的疼痛和疲劳是 参加有效的锻炼计划和日常活动。因此，提高了对 与症状学相关的潜在机制可能导致有效的新方法 管理层。本补充资料将提供执行初步分析以调查潜力的资源 FM的免疫相关机制及其与症状，特别是活动性疼痛的关系。它 已明确免疫系统在FM中起关键作用，其变化与临床症状有关 和活动引起的疼痛。然而，以前的研究在识别特定的免疫细胞类型方面一直含糊其辞。 负责炎症标志物的变化，特别是循环中的细胞因子，通常结果喜忧参半 不同的研究。此外，免疫细胞不是孤立工作的；代谢环境会改变免疫细胞。 表型，免疫细胞可能改变代谢环境，免疫细胞之间的串扰可以 发生。同时，免疫细胞的表观遗传失调直接影响免疫的分化。 细胞表型和亚群。事实上，在FM中观察到了DNA甲基化模式的改变；然而， 目前还不清楚涉及哪些不同的细胞类型。这项提案的主要目标是评估免疫 在单个FM成人队列中使用相对于匹配对照的多种分析来产生飞行员 供将来提交的数据。我们假设免疫系统的变化包括表型 FM患者将发生免疫细胞、IL-1β的诱导释放和单核细胞DNA甲基化的改变 与对照组相比，这些变化与疼痛和疲劳的临床表型有关。我们 进一步提出，细胞因子的变化将与已经收集的代谢组直接相关。 项目。这项研究将通过两个具体目标实现主要目标：目标1：表征免疫系统 在FM和匹配对照组中使用多种技术：1)单核细胞、T细胞、 B细胞和自然杀伤细胞的光谱流式细胞术，2)肌肉代谢产物诱导的释放 单核细胞，以及3)单核细胞DNA甲基化模式和表观遗传年龄；目的2：确定 免疫系统和DNA甲基化变化与临床表型和代谢组的关系 FM患者与匹配对照组的个人资料比较。我们的主要目标将集中在活动诱导 疼痛，次要目的是检查与其他症状的关系，包括疲劳。这项研究将 对FM中潜在的免疫细胞机制提供新的见解。这些新奇的研究有可能 确定与免疫细胞功能相关的诊断性和潜在治疗性FM生物标志物。多种多样- 机构和多学科研究团队在临床和转化科学方面拥有必要的专业知识， 免疫功能和表观遗传学，以有效地利用为父母赠款收集的数据。

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.