Preprint Mapping the Complexity of ME/CFS: Evidence for Abnormal Energy Metabolism, Altered Immune Profile and Vascular Dysfunction, 2025, Heng

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5131664

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder with no known underlying mechanisms, diagnostic tools, or treatments.

Multiple areas of dysfunction have been extensively studied, but rarely examined together.

We recruited age- and sex-matched ME/CFS patients and healthy controls for a multi-modal study examining energy metabolism, immune profiles and plasma protein levels.

Elevated levels of adenosine monophosphate (AMP) were detected in both plasma and immune cells.

Additionally, immune cells showed higher levels of adenosine diphosphate (ADP) and a reduced adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio.

These findings imply decreased ATP generation and the presence of energy stress within the immune cell population.

Adaptive immune cell populations were skewed towards less mature effector subsets of CD4+, CD8+ and gd T cells, and proportions of CD1c+CD141-conventional DC type 2 (cDC2) and CD56lowCD16+ terminal natural killer (NK) cells were also reduced.

Elevated levels of plasma proteins associated with thrombus formation and vascular reactivity may contribute to the endothelial dysfunction observed in ME/CFS patients.

Using Classification and Regression Tree (CART) modelling, we identified variables from each mode of investigation with strong predictive potential for ME/CFS.

Together, this study provides new insights into the somatic symptoms and underlying biology of ME/CFS.

 

Yet another study of inactive PWME vs healthy, active people. I expect they'd find similar differences between couch potatoes and Olympic athletes.