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）是一种使人衰弱的疾病，其特征是深度慢性疲劳，不能通过休息来缓解，以及疼痛，运动后不适，记忆和注意力受损。在美国，ME/CFS影响了超过100万名女性，给患者带来了巨大的痛苦和功能丧失，并给社会带来了巨大的经济负担。由于ME/CFS的潜在病理生理机制尚不清楚，因此没有专门针对该疾病开发的有效治疗方法，许多患者对现有的治疗方案不满意。先前的研究为ME/CFS的炎症参与提供了强有力的证据，尽管在所有研究中没有免疫因素一致地预测疲劳。在低水平或非典型炎症的情况下，传统的横断面研究方法可能不足以识别ME/CFS生物标志物。我们观察到，患有ME/CFS的女性在日常疲劳严重程度上表现出相当大的变异性，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，我们已经确定了一组与ME/CFS 1疲劳变化密切相关的血清细胞因子。在这项拟议的研究中，我们计划在更大的样本中证实我们关于免疫疲劳关系的初步发现。我们将采集70名ME/CFS女性连续25天的血液样本，以及20名健康对照和20名主动疲劳对照（甲状腺功能减退患者）。血液样本将被分析与炎症相关的51种不同免疫因子。此外，参与者将在手持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建立一种区分的生理概况

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.