The hallmark symptom of ME/CFS is post-exertional malaise
(PEM), a worsening of fatigue and other symptoms following physical or mental exercise that can leave patients bedridden for weeks.
The researchers sought to probe microRNAs associated with this symptom, but to spare patients a full-blown bout of PEM in the clinic, Moreau’s team figured out that they could use a therapeutic massager—an inflatable arm cuff that exerts gentle pulsating compressions—to induce a milder form of PEM, as evidenced by headaches, muscle pain, and profound fatigue that patients reported in later questionnaires.
Starting with 11 severely affected, housebound ME/CFS patients, the team drew plasma samples before and 90 minutes after this challenge and screened for differences in levels of microRNAs.
Computational analysis revealed 17 microRNAs whose levels had changed significantly after the test; their response also differed from that of eight age- and sex-matched healthy individuals who had been subjected to the massager but didn’t report any PEM symptoms.
Repeating this analysis in a larger cohort of 32 ME/CFS patients
and 17 matched controls, the team discovered the same response patterns for 11 microRNAs.
In fact, a machine learning algorithm the researchers trained could correctly diagnose someone with ME/CFS based solely on the change in concentration of these microRNAs after the massage intervention. “We were unable to misdiagnose a [healthy] control as ME/CFS, or inversely, ME/CFS as a control,” Moreau says.