Evidence Shows Chronic Fatigue Syndrome Has Biological Basis

Distinct immune changes have been identified in patients diagnosed with chronic fatigue syndrome, known medically as myalgic encephalomyelitis (ME/CFS) or systemic exertion intolerance disease.

The findings could help improve diagnosis and identify treatment options for the disabling disorder, in which symptoms range from extreme fatigue and difficulty concentrating to headaches and muscle pain


Immunologists at the Columbia University's Mailman School of Public Health (New York, NY, USA) used an immunoassay testing methods to determine the levels of 51 immune biomarkers in blood plasma samples collected through two multicenter studies that represented a total of 298 ME/CFS patients and 348 healthy controls. The investigators went to great lengths to carefully screen participants to make sure they had the disease. The team 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 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 and ethnicity/race.

The team used Procarta immunoassays (Affymetrix; Santa Clara, CA, USA) and 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. 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. There are already human monoclonal antibodies on the market that can dampen levels of a cytokine called interleukin-17A that is among those the study shows were elevated in early-stage patients. The only immune factor increased in the whole ME/CFS group versus the controls was leptin. This was highlighted in one network analysis of early duration patients and showed up moderately in two others. The authors noted that it was tightly correlated with most of the immune factors later in the disease but not early.

Mady Hornig, MD, lead author and director of translational research at the Center for Infection and Immunity and associate professor of Epidemiology, said, “We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn't psychological. 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. 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. Early diagnosis may provide unique opportunities for treatment that likely differ from those that would be appropriate in later phases of the illness.” The study was published in the February 2015 issue of the new journal Science Advances.

Related Links:
Columbia University's Mailman School of Public Health
Affymetrix