Benjamin Heng, Bavani Gunasegaran, Shivani Krishnamurthy, Sonia Bustamante, Ananda Staats Pires, Sharron Chow, Seong Beom Ahn, Moumita Paul-Heng, Yolande Maciver, Kirsten Smith, Denise P. Tran, Peter Howley, Ayse Bilgin, Alexandra F. Sharland, Richard Schloeffel, Gilles J. Guillemin
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder with undefined mechanisms, no diagnostic tools and treatments. To investigate concurrent system dysfunctions, we recruited age- and sex-matched ME/CFS patients and healthy controls for a multimodal analysis of energy metabolism, immune profiles, and plasma proteomics. Immune cells from ME/CFS patients show elevated adenosine monophosphate (AMP) and adenosine diphosphate (ADP) with a reduced ATP/ADP ratio, indicating decreased ATP generation and cellular energy stress. Immune profiling reveals skewing toward less mature effector subsets of CD4 + , CD8 + , and γδ T cells, with reduced CD1c + CD141 − conventional DC type 2 and CD56 low CD16 + terminal natural killer cells. Elevated levels of plasma proteins associated with thrombus formation and vascular reactivity may contribute to the endothelial dysfunction observed in ME/CFS patients. Classification and regression tree modeling identifies variables with strong predictive potential for ME/CFS. Together, this study provides insights into the somatic symptoms and underlying biology of ME/CFS.