Australian Study Maps Linked Vascular, Immune, & Energy Changes in ME/CFS
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A newly published, peer-reviewed study from Australia is shedding important light on the biological complexity of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The research, led by scientists at Macquarie University and published in Cell Reports Medicine, provides compelling evidence that ME/CFS involves coordinated abnormalities across energy metabolism, immune function, and vascular biology.
The study, titled Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile and vascular dysfunction, used a sophisticated multi-omics approach to examine multiple biological systems at the same time—something rarely done in previous ME/CFS research.
Researchers analyzed whole blood samples from 61 individuals who met established clinical diagnostic criteria for ME/CFS and compared them with samples from healthy volunteers matched by age and sex. Rather than focusing on a single biological pathway, the team simultaneously assessed cellular energy markers, immune cell composition, and plasma proteins.
One of the most striking findings involved cellular energy production. White blood cells from people with ME/CFS showed elevated levels of adenosine monophosphate (AMP) and adenosine diphosphate (ADP). These changes suggest reduced availability of adenosine triphosphate (ATP), the molecule that powers most cellular processes, pointing to a state of “energy stress” within immune cells.
The immune system itself also appeared altered. Detailed profiling revealed shifts toward less mature forms of several immune cell types, including T lymphocytes, dendritic cells, and natural killer cells. These changes may help explain previously observed immune dysfunction in ME/CFS, but the study’s strength lies in showing how these immune differences coexist with metabolic and vascular abnormalities in the same patients.
In addition, analysis of plasma proteins revealed disruptions related to blood vessel health. Proteins involved in endothelial activation—the inner lining of blood vessels—and vascular remodeling were found at higher levels in people with ME/CFS. At the same time, circulating proteins related to immunoglobulins were lower, suggesting altered immune regulation alongside vascular dysfunction.
Senior author Dr Richard Schloeffel OAM, a Clinical Senior Lecturer at Macquarie Medical School, emphasized the importance of examining these systems together. ME/CFS, he noted, remains a condition with poorly defined mechanisms, limited diagnostic tools, and few effective treatments. Understanding how these biological disruptions interact may be key to improving patient care.
Lead author Dr Benjamin Heng added that while ME/CFS is known to be a heterogeneous condition, studying multiple systems concurrently offers new insight into how these dysfunctions may collectively shape the illness.
Using a machine-learning technique known as classification and regression tree (CART) modeling, the researchers identified a set of seven biological variables that strongly distinguished ME/CFS patients from healthy controls. If validated clinically, such models could eventually help shorten diagnostic delays and reduce the prolonged personal and economic burden experienced by people living with ME/CFS.
Together, these findings reinforce the view of ME/CFS as a complex, multi-system disorder—and highlight the importance of integrated biological research in advancing diagnosis and treatment.