Researchers have found biological similarities underlying five major illnesses long viewed as unrelated: chronic fatigue syndrome, long COVID, PTSD, rheumatoid arthritis and multiple sclerosis. The new study suggests the profound exhaustion common to all five may stem from shared disruptions deep within the body's regulatory networks.
For the study, published in the Journal of Translational Medicine, researchers used Oxford BioDynamics' EpiSwitch Orion platform to examine the three-dimensional architecture of the genome. The team combined published genomic data from existing genome-wide association studies on long COVID, PTSD, rheumatoid arthritis and multiple sclerosis with 3D genomic data from an earlier chronic fatigue syndrome study, without needing to collect new patient samples.
At the level of individual genes, the five conditions—despite being triggered by very different events—showed surprisingly little overlap. But when the researchers analyzed how those genes interact within larger biological networks, a different picture emerged: genes linked to each illness fed into the same core systems, including immune and inflammatory signaling, mitochondrial energy production, metabolic regulation, stress-response mechanisms and neuroendocrine signaling.
The analysis also flagged several "hub genes" sitting at busy points within these shared networks, including LAG3, a molecule tied to "T-cell exhaustion," a state in which immune cells become worn out after prolonged activation.
“We expected to find at least some overlap in genes across the conditions. But we actually found the opposite,” said Dmitry Pshezhetskiy, professor at UEA's Norwich Medical School, who led the study. “This is not something you can see by reading the genetic sequence alone, which is why these conditions may have looked unrelated for so long.”
Because ME/CFS and long COVID currently lack universally accepted laboratory tests and are diagnosed largely through symptoms, the researchers hope the shared biological signatures newly identified could eventually support objective blood tests. The researchers say they hope the shared biological pathways could eventually lead to broader diagnostic tools and even treatments that work across several chronic conditions.
Data from University of East Anglia