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Scientists Discover Robust Evidence That Chronic Fatigue Syndrome Is a Biological Illness

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Note: You can read the full text of the Columbia study HERE.

NEW YORK (Feb. 27, 2015)—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.

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 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.  
Stuck in High Gear
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.” 
Co-authors include Andrew F. Schultz, Xiaoyu Che, and Meredith L. Eddy at the Center for Infection and Immunity; Jose G. Montoya at Stanford University; Anthony L. Komaroff at Harvard Medical School; Nancy G. Klimas at Nova Southeastern University; Susan Levine at Levine Clinic; Donna Felsenstein at Massachusetts General Hospital; Lucinda Bateman at Fatigue Consultation Clinic; and Daniel L. Peterson and Gunnar Gottschalk at Sierra Internal Medicine. The authors report no competing interests.
Support for the study was provided by the Chronic Fatigue Initiative of the Hutchins Family Foundation and the National Institutes of Health (AI057158; Northeast Biodefense Center-Lipkin).
About Columbia University’s Mailman School of Public Health
Founded in 1922, Columbia University’s Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master’s and doctoral degree programs. For more information, please visit www.mailman.columbia.edu.
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Media contact: Tim Paul, Columbia University’s Mailman School of Public Health, 212-305-2676 or tp2111@columbia.edu.

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9 thoughts on “Scientists Discover Robust Evidence That Chronic Fatigue Syndrome Is a Biological Illness”

  1. jayell says:

    Since i have had ME/CFS for over 18 years, and the study only mentions short term or new sufferers, what is being done for those like me? What if any treatment is recommended?

  2. sbrooks says:

    i would love to know how to get in a study or be tested to see if i truly have CFS along with my fibromyalgia. Thank you. Sandra brooks

  3. artseyone says:

    After my diagnosis by a Neurosurgeon, I have chased to find relief. What can be done for us long time sufferers? What hope have we?

  4. ChronicOne says:

    Wow…! Scientists learning how to work a microscope..!
    Yes you can see the pathogen under a microscope. It’s some kind of new Rocket Science apparently.

  5. Dietitian says:

    In my practice as a Registered Dietitian, many patients have come to me with chronic fatigue. Most have additional symptoms such as joint pain, fogginess, and short memory lapses… Usually when the dots don’t connect, it may be Lyme. Sure enough, many test positive without ever seeing a bite. With a functional/integrative approach, many unexplained diseases may have a root cause. Please check for Lyme in those patients with ALS, MS…as well. Google a disease and Lyme (note: Lyme and Epstein Barr) or look on Facebook support groups. Lyme Disease is quite prevalent, yet unrecognized. Also check for a genetic mutation MTHFR.net
    I never thought for a moment that Chronic Fatigue was a psychological illness.
    Any questions EMetzgerRD@me.com

  6. renoredhead says:

    I was diagnosed with CFS/Fibromyalgia 23 years ago. After the first 3 years, I did get much better. That lasted until a couple of years ago, when I experienced a sudden, severe relapse, though at this point, I’m not sure where to draw the line between CFS and FM on my symptoms.

    I’m hoping there will be diagnostic help for us as well … I have been fighting with Social Security for a few years now, since I cannot even work a couple of hours a few days a week.

  7. Otowner says:

    Only two testing facilities in the U.S. can accurately diagnose chronic Lyme disease. IGenX is one, but I’ve forgotten the name of the other. Chronic Lyme and some of it’s co-infections mimic Fibromyalgia and CFS/ M.E. So does heavy metal poisoning (mercury poisoning) and parasite infections. Google the Lyme documentary “Under our skin” (free to watch online), and various videos by Dr. Andreas Kalcker for information on parasites. There’s a strange cover up going on with Lyme, and it’s causing hundreds of thousands of people to suffer needlessly.

  8. Angel111 says:

    At long last sufferers might be taken seriously. I was wondering if this information has been distributed to GP’S everywhere and if the GP’S attend training for treating patients with this Condition? By the way I am living in Cork, Ireland.I sometimes wonder if this type of information is distributed to America and the UK only! Kind regards, Angel

  9. islandflower61 says:

    while you are testing people who are only 3 yrs into this disease what can be done for those of us who have already had this disease long term? i was diagnosed with fibro in 2006.I get mono at least 3-4 reoccuring times a year! this is not a disease most doctors except as a diagnosis. my new pcp a young doctor was not excepting untill i showed him all tests all my illnesses and previous treatments i have tried. the public needs more awareness as well as doctors need to be educated that this is and illness not a mental problem. I have educated my new doctor and opened his eyes to help others.

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