Scientists at Columbia University’s Mailman School of Public Health have identified a unique pattern of immune molecules in the cerebrospinal fluid of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that provides insights into the basis for cognitive dysfunction—frequently described by patients as “brain fog”—as well as new hope for improvements in diagnosis and treatment.
The study, by Prof Mady Hornig, Prof Ian Lipkin and colleagues used immunoassay testing methods to measure levels of 51 immune biomarkers called cytokines in the cerebrospinal fluid of 32 people with ME/CFS for an average of seven years, 40 with multiple sclerosis, and 19 non-diseased controls.
“Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.”
The researchers found that levels of most cytokines, including the inflammatory immune molecule interleukin 1, were depressed in individuals with ME/CFS compared with the other two groups, matching what was seen in a blood study in patients who had the disease for more than three years. One cytokine—eotaxin—was elevated in the ME/CFS and MS groups, but not in the control group.
The study was the second to be supported by a grant from the Chronic Fatigue Initiative of the Hutchins Family Foundation and the Edward P. Evans Foundation.
In the first study, the researchers discovered distinct plasma immune signatures in the early stages of ME/CFS, supporting the idea that ME/CFS may reflect an infectious ‘hit-and-run’ event.
“We now know that the same changes to the immune system that we recently reported in the blood of people with ME/CFS with long-standing disease are also present in the central nervous system,” says Dr. Hornig, professor of Epidemiology and director of translational research at the Center for Infection and Immunity at the Mailman School. “These immune differences may contribute to symptoms in both the peripheral parts of the body and the brain, from muscle weakness to brain fog.”
Implications for Diagnosis and Treatment
“Diagnosis of ME/CFS is now based on clinical criteria. Our findings offer the hope of objective diagnostic tests for disease as well as the potential for therapies that correct the imbalance in cytokine levels seen in people with ME/CFS at different stages of their disease,” adds W. Ian Lipkin, MD, John Snow Professor of Epidemiology and director of the Center for Infection and Immunity.
There is precedent for use of human monoclonal antibodies that regulate the immune response in a wide range of disorders from rheumatoid arthritis to multiple sclerosis. However, the researchers note, additional work will be needed to assess the safety and efficacy of this approach.
PHOTOS: (L) Exercise Plays Vital Role… by A Health Blog, (R) Mady Hornig, M.D., lead author and director of translational research at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health.
Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Hornig M, Gottschalk G, Peterson DL, Knox KK, Schultz AF, Eddy ML, Che X, Lipkin W.
Primary address: Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, USA.
Publication: Molecular Psychiatry, 2015 March 31
Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay.
Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1β, suggesting a disturbance in interleukin 1 signaling.
Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.
- Scientists find clues into cognitive dysfunction in chronic fatigue syndrome, ME Research UK, Mar 31, 2015, [press release]
- Hornig M, Gottschalk G, Peterson DL, Knox KK, Schultz AF, Eddy ML, Che X, Lipkin W., (2015) Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome, Mol Psychiatry. 2015 Mar 31. doi: 10.1038/mp.2015.29. [PubMed]