Researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health identified distinct immune changes 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.
[Photo: Dr. Mady Hornig (above) and Dr. W. Ian Lipkin]
These immune signatures represent the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder, and the first evidence that the disease has distinct stages. Results appear online in the new American Association for the Advancement of Science journal, Science Advances.
With funding to support studies of immune and infectious mechanisms of disease from the Chronic Fatigue Initiative of the Hutchins Family Foundation, the researchers used 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. 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. 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.
“We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn’t psychological,” states lead author Dr. Mady Hornig, 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.”
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. Before any drugs can be tested in a clinical trial, Dr. Hornig and colleagues hope to replicate the current, cross-sectional results in a longitudinal study that follows patients for a year to see how cytokine levels, including interleukin-17A, differ within individual patients over time, depending on how long they have had the disease.
In 2012, Dr. W. Ian Lipkin, director of the Center for Infection and Immunity, and colleagues reported the results of a multicenter study that definitively ruled out two viruses thought to be implicated in ME/CFS: XMRV (xenotropic murine leukemia virus [MLV]-related virus) and murine retrovirus-like sequences (designated pMLV: polytropic MLV). In the coming weeks, Drs. 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—be they viral, bacterial, or fungal—as well as the longitudinal look at how plasma cytokine patterns change within ME/CFS patients and controls across a one-year period, as noted above.