Daily Immune Monitoring in Chronic Fatigue Syndrome

慢性疲劳综合症的日常免疫监测

• 批准号: 8927153
• 负责人: Jarred W. Younger
• 金额: $ 22.48万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8927153
• 关键词: Affect; Age; Animals; Bed rest; Behavioral; Biochemical; Biological; Biological Markers; Blood; Blood Screening; Blood specimen; Caring; Chronic; Chronic Fatigue Syndrome; Clinical; Control Groups; Cross-Sectional Studies; Data Set; Development; Devices; Diagnosis; Diagnostic tests; Diet; Disease; Distress; Eotaxin; Event; Fatigue; Flare; Functional disorder; Future; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Handheld Computers; Health; Health Expenditures; Human; Hypothyroidism; Immune; Immune Sera; Immunologic Markers; Immunologic Monitoring; Impairment; Individual; Inflammation; Inflammatory; Intercellular adhesion molecule 1; Interferon-alpha; Interleukin-6; Intervention; Leptin; Machine Learning; Malaise; Mediating; Memory; Modeling; Monitor; Pain; Participant; Pathology; Pathway interactions; Patients; Physiological; Process; Productivity; Protocols documentation; Psychological Stress; Reporting; Research; Research Personnel; Rest; Sampling; Serum; Severities; Signal Transduction; Sleep; Societies; Specimen; Subgroup; Syndrome; Techniques; Time; Transforming Growth Factor alpha; United States; Woman; base; cohort; cost; cytokine; effective therapy; experience; improved; interest; loss of function; men; novel strategies; resistin; tool

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.

描述（由申请人提供）：肌电脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种令人衰弱的疾病，其特征是深度，慢性疲劳，不受休息以及疼痛，后疗法的不适以及记忆和集中的损害。 ME/CF在美国影响超过100万妇女，导致受影响的个体的严重困扰和功能丧失，并且对社会产生了巨大的财务负担，因为ME/CFS的潜在病理生理学并没有得到充分理解，因此没有针对这种病情的有效治疗，许多患者对现有治疗方案不满意。以前的研究为ME/CFS的炎症介入提供了有力的案例，尽管没有免疫因素始终如一地预测整个研究的疲劳。在低水平或非典型炎症的情况下，常规的横断面研究方法可能不足以识别ME/CFS生物标志物。我们已经观察到，与我/CFS的女性在疲劳严重程度上表现出很大的日常变异性，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重要信号，并每天收集血液样本，我们已经确定了一系列与ME/CFS 1FATIGUE变化密切相关的血清细胞因子。在这项拟议的研究中，我们计划在较大样本中确认我们对免疫效果关系的初步发现。我们将连续25天收集70名ME/CF的女性，以及20个健康对照和20种主动疲劳对照（患有甲状腺功能减退症的个体）。将分析与炎症相关的51种不同免疫因子的血液样本。此外，参与者将每天在手持计算机上提交有关疲劳严重程度的报告。通过纵向分析疲劳评分和细胞因子浓度，我们可以确定疲劳严重程度“跟踪”日常波动的细胞因子。这种方法将使我们能够开发出区分的生理特征 低疲劳日的高疲劳日，提供有关ME/CFS机制的重要信息。在AIM 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准确预测疲劳严重程度的日常波动。在AIM 2中，我们将根据细胞因子效果关系定义重要的ME/CFS子组。在AIM 3中，我们将在免疫因子和疲劳之间发展一个时间途径，以确定疲劳的早期驱动因素。此外，我们将开发一个可以向其他感兴趣的研究人员提供的血液样本标本。密集的纵向免疫监测是理解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出色的目标。