Daijiworld Media Network - New Delhi
New Delhi, Sep 3: A new study has identified a shared biological process that may help explain chronic exhaustion across five conditions — post-traumatic stress disorder (PTSD), long Covid, rheumatoid arthritis (RA), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS).
The findings, published in the Journal of Translational Medicine, reveal “striking” biological similarities between illnesses traditionally viewed as separate disorders and triggered by different factors, ranging from viral infections and psychological trauma to autoimmune responses.
Researchers led by scientists from the University of East Anglia and Oxford BioDynamics Plc in the UK found that genes associated with each condition were feeding into the same major biological systems. These included immune and inflammatory signalling, mitochondrial energy production, metabolic regulation, stress-response mechanisms and neuroendocrine signalling.
The findings could help explain why people who experience a viral infection or psychological trauma can go on to develop similar symptoms, the researchers said.
“We now think the answer may lie in shared regulatory networks embedded within the body's immune and metabolic systems,” lead researcher Dmitry Pshezhetskiy, professor at the University of East Anglia's Norwich Medical School, said.
“A COVID-19 infection may trigger prolonged immune activation. Traumatic stress may disrupt stress-hormone pathways and inflammatory responses. But both disturbances appear capable of converging on common biological circuits controlling energy production, immune regulation and cellular resilience,” Pshezhetskiy said.
“When those systems become persistently dysregulated, the result may be the profound and disabling fatigue seen across multiple disorders,” he added.
The researchers analysed DNA sequences using Oxford BioDynamics' EpiSwitch Orion platform, which examines the three-dimensional architecture of the genome and studies how DNA folds and interacts inside living cells.
The computational analysis examined published genomic data on long Covid, PTSD, rheumatoid arthritis and multiple sclerosis from previous studies. These were combined with three-dimensional genomic data from an earlier ME/CFS patient study, without requiring the collection of new patient samples.
“DNA is folded in our cells, so regions far apart in the linear sequence can touch, and those contact points are where genes get controlled. Orion predicts where these contact points are likely to be,” Ewan Hunter, chief data officer at Oxford BioDynamics, said.
When applied across the five conditions, Orion found that genetic changes that appeared to have little in common were connected to the same regulatory circuitry.
Pshezhetskiy said researchers had expected to find at least some overlap in genes across the conditions, but instead found surprisingly little direct overlap at the individual gene level.
“At an individual gene level, there was surprisingly little direct overlap between long Covid, ME/CFS, PTSD, multiple sclerosis and rheumatoid arthritis. But when we analysed how those genes interact in complex biological networks, a completely different picture emerged. Suddenly, the diseases appeared deeply connected,” he said.
“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,” Pshezhetskiy said.
The researcher explained that while the conditions may be triggered by completely different events, they ultimately disrupt the same fundamental biological systems and produce similarly devastating exhaustion experienced by millions worldwide.
“Despite limited genetic overlap, substantial convergence at the network level suggests shared biological architecture across ME/CFS, LC19 (long Covid), PTSD, RA (rheumatoid arthritis), and MS (multiple sclerosis),” the authors wrote.