Abstract:
Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
摘要:
感染后肌痛性脑脊髓炎/慢性疲劳综合征(PI-ME/CFS)是一种致残性疾病,然而临床表型定义不清,病理生理学是未知的,并且没有疾病改善的治疗方法。我们使用严格的标准招募具有匹配对照的PI-ME/CFS参与者进行深度表型鉴定。在许多身体和认知方面的抱怨中,PI-ME/CFS的一个定义特征是努力偏好的改变,而不是身体或中枢疲劳,由于可能与中枢儿茶酚途径失调相关的整合脑区功能障碍,对自主神经功能和身体条件有影响。免疫谱分析提示慢性抗原刺激,初始免疫增加,转换记忆B细胞减少。外周血单个核细胞基因表达谱和代谢途径的改变与细胞表型研究一致,并根据性别显示出差异。这些临床异常和生物标志物差异共同为PI-ME/CFS的潜在病理生理学提供了独特的见解。这可能会指导未来的干预。