Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

ME/CFS is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we used single-cell RNA-seq (scRNA-seq) to examine immune cells in cohorts of patients and controls. Post-exertional malaise (PEM), an exacerbation of symptoms following exercise, is a characteristic symptom of ME/CFS. Thus, to detect changes coincident with PEM, we also performed scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients displayed dysregulation of classical monocytes suggestive of inappropriate differentiation and migration to tissue. We were able to identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlated with metrics of disease severity. Comparing the transcriptome at baseline and post-exercise challenge, we discovered patterns indicative of improper platelet activation from 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 following strenuous exercise. Overall design: Blood samples were collected from 30 ME/CFS cases and 28 age- and activity-matched controls at two timepoints: prior to a cardiopulmonary exercise test (CPET) and 24h later. PBMCs were isolated and gene expression was profiled using the 10x Genomics single-cell RNAseq platform.