Daily Immune Monitoring in Chronic Fatigue Syndrome

描述（由申请人提供）：肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种衰弱性疾病，其特征为休息无法缓解的严重慢性疲劳，以及疼痛、运动后不适和记忆力和注意力障碍。ME/CFS在美国影响超过一百万女性，在受影响的个体中造成显著的痛苦和功能丧失，并对社会造成重大的经济负担。先前的研究为ME/CFS中的炎症参与提供了强有力的案例，尽管没有免疫因素在研究中始终预测疲劳。传统的横断面研究方法可能不够敏感，以确定ME/CFS生物标志物的情况下，低水平或非典型炎症。我们观察到，患有ME/CFS的女性的疲劳严重程度表现出相当大的日常变异性，这种变异性可能反映了潜在疾病机制的快速变化。通过将每日疲劳变异性视为一个重要信号，并每天收集血液样本，我们已经确定了一小部分血清细胞因子与ME/CFS 1疲劳的变化密切相关。在这项拟议的研究中，我们计划在更大的样本中证实我们对免疫疲劳关系的初步发现。我们将连续25天收集70名ME/CFS女性以及20名健康对照和20名主动疲劳对照（甲状腺功能减退症患者）的血液样本。将分析血液样本中与炎症相关的51种不同免疫因子。此外，参与者将在掌上电脑上提交疲劳严重程度的每日报告。通过纵向分析疲劳评分和细胞因子浓度，我们可以确定细胞因子，“跟踪”疲劳严重程度的日常波动。这种方法将使我们能够开发出一种生理特征， 从低疲劳天的高疲劳天，提供有关ME/CFS机制的重要信息。在目标1中，我们将开发一种生理模型，该模型使用血清细胞因子水平来准确预测疲劳严重程度的日常波动。在目标2中，我们将根据疲劳-疲劳关系定义重要的ME/CFS亚组。在目标3中，我们将开发免疫因素和疲劳之间的时间通路，以识别疲劳的早期驱动因素。此外，我们将开发一个血液样本标本库，可供其他感兴趣的研究人员使用。强化纵向免疫监测是了解ME/CFS病理生理学的独特方法。这项研究揭示的生物标志物将作为ME/CFS诊断测试开发的工具，并将为开发改进的疗法提供极好的靶点。

DESCRIPTION (provided by applicant): Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition characterized by profound, chronic fatigue that is not alleviated by rest, as well as pain, post-exertional malaise, and impairments in memory and concentration. ME/CFS affects over one million women in the United States, causing significant distress and loss of function in affected individuals and a significant financial burden on society Because the underlying pathophysiology of ME/CFS is not well-understood, there are no effective treatments developed specifically for the condition, and many patients are unsatisfied with existing treatment options. Previous research provides a strong case for inflammatory involvement in ME/CFS, though no immune factors have been consistently predictive of fatigue across studies. Conventional cross-sectional research approaches may not be sufficiently sensitive for identifying ME/CFS biomarkers in cases of low-level or atypical inflammation. We have observed that women with ME/CFS demonstrate considerable day-to-day variability in their fatigue severity, and this variability may reflect rapid shifts in underlying disease mechanisms. By viewing the daily fatigue variability as an important signal, and collecting blood samples daily, we have identified a small set of serum cytokines that are strongly correlated with changes in ME/CFS 1fatigue. In this proposed study, we plan to confirm our preliminary findings of immune-fatigue relationships in a larger sample. We will collect blood samples for 25 consecutive days in 70 women with ME/CFS, as well as 20 healthy controls and 20 active fatigue controls (individuals with hypothyroidism). Blood samples will be analyzed for 51 different immune factors associated with inflammation. In addition, participants will submit daily reports of fatigue severity on handheld computers. By analyzing fatigue scores and cytokine concentrations longitudinally, we can identify cytokines that "track" day-to-day fluctuations in fatigue severity. This approach will allow us to develop a physiological profile that distinguishes high fatigue days from low fatigue days, providing important information about ME/CFS mechanisms. In Aim 1, we will develop a physiological model that uses serum cytokine levels to accurately predict day-to-day fluctuations in fatigue severity. In Aim 2, we will define important ME/CFS subgroups based on cytokine-fatigue relationships. In Aim 3, we will develop a temporal pathway between immune factors and fatigue that identifies early drivers of fatigue. Additionally, we will develop a specimen bank of blood samples that can be made available to other interested researchers. Intensive longitudinal immune monitoring is a unique approach to understanding ME/CFS pathophysiology. Biomarkers revealed by this research will serve as tools in the development of ME/CFS diagnostic tests, and will provide excellent targets for developing improved therapies.