Cell-free RNA in Plasma
We will examine the cell-free RNA (cfRNA) molecules present in the circulation at all four time points when blood was collected during the first phase of our NIH Center (2017–2023).
Plasma samples from 173 subjects who underwent the two-day exercise test have been banked for use.
Ninety-one ME/CFS patients and 82 age- and gender-matched sedentary controls performed two successive cardiopulmonary exercise tests (CPETs), separated by 24 hours. Blood samples were collected at four time points: baseline before the first CPET (preDay1), 15 minutes after the first CPET (postDay1), after a 24-hour recovery period (preDay2), and 15 minutes after the second CPET (postDay2).
CfRNA is released from both solid tissues and immune cells as a result of cell death. One way to assess the proportion of cell types that are turning over is to determine the source of cfRNA. The cellular source of cfRNA in each subject can be identified by comparing it with known patterns of differential gene expression in different cell types.
Our premise is that identifying the cell types of origin of cfRNA in ME/CFS patients and controls before and after exercise may provide clues to the disruptions that occur when people with ME/CFS elevate their activity levels. In particular, learning which cell types have altered patterns of injury and cell death in ME/CFS may reveal immune and tissue involvement in the pathophysiology of post-exertional malaise (PEM).
Dr. Iwijn De Vlaminck’s group in the Meinig School of Biomedical Engineering is responsible for cell-free RNA analysis.
Current Publication
Our team recently published the first findings from this project, focusing on baseline cfRNA analysis. This study identified distinct molecular signatures that may help characterize and diagnose ME/CFS, even prior to any exercise challenge. These findings represent an important foundation for our ongoing work examining how cfRNA patterns shift following exercise, which may further clarify the biological mechanisms underlying post-exertional malaise.
Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome. Gardella AE, Eweis-LaBolle D, Loy CJ, Belcher ED, Lenz JS, Franconi CJ, Scofield SY, Grimson A, Hanson MR, De Vlaminck I. Proc Natl Acad Sci U S A. 2025 Aug 19;122(33):e2507345122.