New research has identified distinct immune changes in patients diagnosed with chronic fatigue syndrome, providing evidence that the disabling disorder is a biological illness as opposed to a psychological disorder.
According to researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health, the findings could help improve diagnosis of chronic fatigue syndrome, known medically as myalgic encephalomyelitis (ME/CFS) or systemic exertion intolerance disease.
They also could help identify treatment options for the disorder’s symptoms, which range from extreme fatigue and difficulty concentrating to headaches and muscle pain.
For their study, researchers used immunoassay testing methods to determine the levels of 51 immune biomarkers in blood plasma samples collected from 298 ME/CFS patients and 348 healthy people as controls.
The researchers report they found specific patterns in patients who had the disease three years or less that were not present in controls or in patients who had the disease for more than three years.
The short duration patients had increased amounts of many different types of immune molecules called cytokines. The association was unusually strong with a cytokine called interferon gamma that has been linked to the fatigue that follows many viral infections, including Epstein-Barr virus (the cause of infectious mononucleosis). Cytokine levels were not explained by symptom severity, the researchers noted.
“We now have evidence confirming what millions of people with this disease already know — that ME/CFS isn’t psychological,” said lead author Mady Hornig, M.D., director of translational research at the Center for Infection and Immunity and associate professor of epidemiology at Columbia’s Mailman School.
“Our results should accelerate the process of establishing the diagnosis after individuals first fall ill, as well as discovery of new treatment strategies focusing on these early blood markers.”
The study supports the idea that ME/CFS may reflect an infectious “hit-and-run” event, the researchers noted.
Patients often report getting sick, sometimes from something as common as infectious mononucleosis, and never fully recover.
The new research suggests that these infections throw a wrench in the immune system’s ability to quiet itself after the acute infection. Researchers compare the immune response to a car stuck in high gear.
“It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,” said Hornig.
“Early diagnosis may provide unique opportunities for treatment that likely differ from those that would be appropriate in later phases of the illness.”
The researchers noted they went to great lengths to carefully screen participants to make sure they had the disease. They also recruited greater numbers of patients whose diagnosis was of relatively recent onset.
Patients’ stress levels were standardized; before each blood draw, patients were asked to complete standardized paperwork, in part to engender fatigue, the researchers explained. The scientists also controlled for factors known to affect the immune system, including the time of day, season and geographic location where the samples were taken, as well as age, sex, ethnicity, and race.
“This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in ME/CFS and diagnostic biomarkers for disease,” said senior author W. Ian Lipkin, M.D., also a professor of epidemiology at Columbia’s Mailman School.
“The question we are trying to address in a parallel microbiome project is what triggers this dysfunction.”
In the coming weeks, Hornig and Lipkin expect to report the results of a second study of cerebrospinal fluid from ME/CFS patients. In separate ongoing studies, they are looking for “molecular footprints” of the specific agents behind the disease — viral, bacterial, or fungal — as well as a longitudinal look at how plasma cytokine patterns change within ME/CFS patients and controls over a year.
The current study was published in Science Advances, the journal of the American Association for the Advancement of Science.