US scientists claim ‘robust evidence’ that ME/CFS is a biological illness | Columbia University press release | 27 February 2015

February 27, 2015

Click on the link to read the full paper: Distinct plasma immune signatures in ME/CFS are present early in the course of illness

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).

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.

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.

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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 Mady Hornig, MD, 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.


The study supports the idea that ME/CFS may reflect an infectious “hit-and-run” event. Patients often report getting sick, sometimes from something as common as infectious mononucleosis (Epstein-Barr virus), 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, to return to a homeostatic balance; the immune response becomes like 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,” says Dr. 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 investigators went to great lengths to carefully screen participants to make sure they had the disease. The researchers 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.

In 2012, W. Ian Lipkin, MD, 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.

“This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in ME/CFS and diagnostic biomarkers for disease,” says senior author W. Ian Lipkin, MD, also the John Snow 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.”

Click on the link to read the full paper: Distinct plasma immune signatures in ME/CFS are present early in the course of illness

Expert reaction to biomarkers for CFS/MEopinions assembled for journalists by the Science Media Centre.


We were disappointed to see that immunologists were not among the experts asked by the Science Media Centre to comment on this weekend's big M.E. research paper. We are very pleased that scientists from outside the field were approached, and are building on this by asking other researchers to give their view. We are working with Action for ME on a joint approach.

4 thoughts on “US scientists claim ‘robust evidence’ that ME/CFS is a biological illness | Columbia University press release | 27 February 2015”

  1. What about the dangers of immune suppression from antii-inflammatories in cases of ongoing infection? Absence of ongoing infection is by no means proven across the patient population, misdiagnosis occurs e.g. Lyme cases missed, opportunists such as candida ignored.
    Further at later stages where the immune system is exhausted will antiinflammatories not be counterindicated.

  2. Interesting to see how many of the psychiatrists views are in the SMC and the declared interests at the bottom!!

  3. This is not the first study demonstrating a biological basis to CFS, the Charité – Universitätsmedizin Berlin published a research paper on PLOS ONE over a year ago, demonstrating that in a subset of CFS sufferers, there is a, “Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome”. In essence, some of those who have had glandular fever never develop specific immunity to the virus, so their immune systems are constantly having to fight latent replication of it.

    Furthermore, Prof. Dr. Carmen Scheibenbogen, of the previous research team, reports of her latest research project, “We develop diagnostic marker for CFS based on the dysregulated immune response againgst EBV”, yet to be published.

    I would speculate that other viruses could provoke a similar pathological non-response from their immune systems: for example, Dr Charles Sheperd’s condition was triggered by Chicken Pox. It is noteworthy that CFS affects females and those who are adolescent or older; I would further speculate that the juvenile immune system with its fully functional thymus is better at coping with juvenile illnesses and that adolescence potentially reduces the effective immune response, particularly in females whose immune systems are reprioritised for pregnancy.

  4. So my question would be, what happens *after* three years? How are the ongoing symptoms (which in my experience don’t differ greatly from those up to three years) caused?

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