Correlating neutrophil function and plasma cytokine profiles with progression of ME/CFS and Long-Covid/PASC

将中性粒细胞功能和血浆细胞因子谱与 ME/CFS 和 Long-Covid/PASC 的进展相关联

基本信息

  • 批准号:
    10572843
  • 负责人:
  • 金额:
    $ 25.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-12-05 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

SUMMARY Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS) is a complex chronic condition associated with prolonged inflammatory signaling. Long Covid/Post-Acute Sequelae of Covid (PASC) has been noted as a relatively common outcome of SARS-CoV-2 infection, and appears to mirror many of the features of ME/CFS, suggesting that the etiology of these conditions might be shared [1, 2]. Neutrophils are the most common immune cells in the circulation and are exquisitely sensitive to changes in inflammatory signaling. We have developed a unique panel of microfluidic assays that probe neutrophil function from a drop of fresh blood. We recently used these assays on fresh fingerpick blood obtained from 6 ICC-diagnosed ME/CFS subjects and 1 PASC subject and found preliminary evidence that multiple neutrophil functions were altered in ME/CFS relative to progression of disease. Strikingly, the PASC subject exhibited changes in neutrophil function most similar to early-stage ME/CFS. The goal of our project is to use these microfluidic assays to probe neutrophil function in a larger cohort of ICC-ME/CFS, PASC subjects, and healthy controls. We will characterize neutrophil motility and extracellular trap formation (NETosis) from a drop of fresh blood, both at baseline and following in vitro stimulation, in all subjects. We will also use an established panel to characterize proinflammatory cytokines in ME/CFS, PASC, and healthy control subject blood collected at the same time as the neutrophil fingerprick samples. This will determine if proinflammatory cytokine burden will correlate with neutrophil motility and baseline NETosis across groups. An overarching aim of the proposal is to analyze neutrophil responses as a function of illness duration in both ME/CFS and PASC. Characterization of neutrophil behavior in relatively recent-onset PASC will lay the groundwork for future longitudinal studies of this condition and will help determine the mechanistic overlap with ME/CFS or lack thereof.
总结 肌痛性脑病/慢性疲劳综合征(ME/CFS)是一种复杂的慢性疾病, 延长炎症信号传导。新型冠状病毒长期/急性后遗症(PASC)已被视为 SARS-CoV-2感染的相对常见的结果,似乎反映了ME/CFS的许多特征, 这表明这些疾病的病因可能是共同的[1,2]。中性粒细胞是最常见的免疫 细胞在循环中,并对炎症信号的变化非常敏感。我们已经开发出一种 独特的微流控检测面板,从一滴新鲜血液中探测中性粒细胞功能。我们最近使用了 这些测定是对从6名ICC诊断的ME/CFS受试者和1名PASC受试者中获得的新鲜手指采血进行的 并发现初步证据表明,相对于对照组,ME/CFS患者的多种中性粒细胞功能发生了改变。 疾病进展。令人惊讶的是,PASC受试者表现出的中性粒细胞功能变化与 早期ME/CFS。我们的项目的目标是使用这些微流控检测来探测中性粒细胞的功能, ICC-ME/CFS、PASC受试者和健康对照的较大队列。我们将描述中性粒细胞运动 和细胞外陷阱形成(NETosis)从一滴新鲜血液,无论是在基线和体外 刺激,在所有科目。我们还将使用一个已建立的面板来表征促炎细胞因子, ME/CFS、PASC和健康对照受试者的血液在中性粒细胞手指针刺的同时采集 样品这将确定促炎性细胞因子负荷是否与中性粒细胞运动和基线相关。 跨组NETosis。该提案的首要目标是分析中性粒细胞反应作为以下功能的函数: ME/CFS和PASC中的疾病持续时间。相对近期发病的中性粒细胞行为特征 PASC将为今后对这种情况的纵向研究奠定基础,并将帮助确定 与ME/CFS的机制重叠或缺乏重叠。

项目成果

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