Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing
Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing
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DOI：
10.1371/journal.pone.0212193
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发表时间：
2019-03-21
期刊：
影响因子：
3.7
通讯作者：
Chiu, Charles Y.
中科院分区：
文献类型：
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作者：
Bouquet, Jerome;Li, Tony;Chiu, Charles Y.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种病因不明的综合征，其特征是体力活动加剧的深度疲劳，也称为运动后不适（PEM）。以前，我们没有检测到免疫失调或病毒再激活的PEM时期以外的证据。在此，我们试图确定ME/CFS患者的心肺运动负荷试验是否会引发这种变化。ME/CFS患者（n = 14）和匹配的久坐对照（n = 11）连续2天进行心肺运动，并在运动后随访7天，并通过RNA-seq分析纵向全血样品。尽管ME/CFS患者在运动后症状与对照组相比显著恶化，14名ME/CFS患者中有8名在第2天显示出减少的耗氧量（V超过dotO（2）），但当在所有时间点将ME/CFS患者与对照组进行比较时，转录组分析仅产生6个差异表达基因（DEG）候选者。ME/CFS患者运动前后的DEG均不与免疫信号有关。病毒组组成（卡方检验P = 0.746）和病毒读数数量（配对t检验P = 0.098）与PEM无显著相关性。这些观察结果不支持ME/CFS患者在症状性PEM发作期间转录介导的免疫细胞失调或病毒再活化。
Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ((V) over dotO(2)) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.