Iu et al. (2025)
- Authors: David S. Iu, Faraz Ahmed, Elizabeth Fogarty, Carl Franconi, Jennifer Grenier, Maureen Hanson, Andrew Grimson
- Institutes: Cornell University, Ithaca, NY, USA
- Publisher: The Journal of Immunology
- Link: DOI
Summary
This research identifies a specific subpopulation of immune cells that appears to be a primary driver of inflammation in ME/CFS. By pinpointing exactly which cells are ‘reprogrammed’ at the epigenetic level, the study provides a concrete target for future diagnostic tests and treatments aimed at stopping the inflammatory response that causes symptoms like post-exertional malaise.
What was researched?
The study investigated how the gene regulatory landscape and chromatin accessibility of immune cells are reshaped in ME/CFS patients, particularly during post-exertional malaise (PEM).
Why was it researched?
While previous studies identified general immune dysregulation in ME/CFS, it remained unclear which specific cell subsets were responsible for driving inflammation and how their internal ‘genetic switches’ were altered during symptom flares.
How was it researched?
Researchers generated single-cell chromatin accessibility profiles (scATAC-seq) and transcriptomic data from peripheral blood mononuclear cells (PBMCs) of patients and healthy controls. These samples were collected both at baseline and after an exercise-induced PEM provocation to capture changes in real-time.
What has been found?
The researchers identified a unique subpopulation of classical monocytes characterized by reduced CD14 accessibility and increased accessibility near pro-inflammatory genes. These specific genes were found to be significantly upregulated in ME/CFS patients. Additionally, the study observed widespread epigenetic reprogramming at transcription factor binding sites, particularly involving the NF-kappa-B (NF-κB) family in monocytes.
Discussion
The findings suggest that ME/CFS is characterized by a persistent state of monocyte activation that is etched into the cells’ epigenome. This epigenetic ‘priming’ likely explains why patients react so strongly to physical exertion.
Conclusion & Future Work
The discovery of a distinct, inflammatory monocyte subset provides a new biomarker for ME/CFS pathology. Future research should focus on whether these epigenetic changes can be reversed to alleviate systemic inflammation.