Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Genomics Innovation Hub and TREx Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14853, USA.
Cell Rep Med. 2024 Jan 16;5(1):101373. doi: 10.1016/j.xcrm.2023.101373.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.
肌痛性脑脊髓炎/慢性疲劳综合征 (ME/CFS) 是一种严重且尚未被充分了解的疾病。为了了解 ME/CFS 中的免疫失调，我们使用单细胞 RNA 测序 (scRNA-seq) 来检查患者和对照队列中的免疫细胞。运动后不适 (PEM) 是 ME/CFS 的一种特征性症状，即在剧烈运动后症状加重。为了检测与 PEM 同时发生的变化，我们在运动后对相同的队列进行了 scRNA-seq 分析。在基线时，ME/CFS 患者表现出典型的单核细胞失调，提示分化和向组织迁移不当。我们在患者体内同时鉴定出患病和更正常的单核细胞，患病细胞的比例与疾病严重程度相关。比较基线时和运动后挑战时的转录组，我们发现患者血小板激活异常的模式，而免疫系统的其他部位变化很小。总之，这些数据表明患者在基线时存在免疫缺陷，以及血小板的另外一层失调。
