The cerebrospinal fluid (CSF) circulates in the subarachnoid space around the brain and spinal cord

The cerebrospinal fluid (CSF) circulates in the subarachnoid space in the brain and spinal cord

In a press release today, Columbia University’s Mailman School of Public Health reports that its scientists have identified “a unique pattern of immune molecules in the cerebrospinal fluid of people with ME/CFS”, raising hopes of improvements in diagnosis and treatment. The study, published in Molecular Psychiatry, is the second published by Prof Mady Hornig, Prof Ian Lipkin and colleagues with funding from Chronic Fatigue Initiative of the Hutchins Family Foundation and the Edward P. Evans Foundation. In the first (Science Advances, February 2015), 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.

In their latest series of experiments, the scientists used immunoassay testing methods to measure levels of 51 cytokines (immune proteins important in cell signalling) in the cerebrospinal fluid of 32 ME/CFS patients who had been ill for 7.6 years on average; 40 multiple sclerosis (MS) patients; and 19 controls without obvious disease. Cerebrospinal fluid samples were obtained from biobanks at either Sierra Internal Medicine (SIM) in Nevada, or the University of California Los Angeles (UCLA) Brain Bank. Importantly, MS patients were included as a comparison group, given that the disease shares the symptom of fatigue with ME/CFS (see review), and that abnormalities to cytokines are known to occur in the cerebrospinal fluid of MS patients.

The researchers found that levels of many pro- and anti-inflammatory cytokines, including the inflammatory immune molecule interleukin 1, were lower in people with ME/CFS than in the healthy controls. In addition, immune profiles differed between the ME/CFS and MS patients: immune activation in the central nervous system was greater in ME/CFS than MS, while levels of other cytokines were reduced. On logistic regression modelling, one cytokine – CCL11 (eotaxin, involved in the recruitment of some kinds of white blood cells) – was very strongly elevated in the ME/CFS group compared with the controls, while levels of interleukin 1beta were lower. By contrast, compared with MS, ME/CFS was associated with markedly higher TGFbeta levels, with higher CCL2 levels, and with decreased levels of VCAM1. Most interesting, perhaps, are the results of the classification and regression tree (CART) analyses which suggest the existence of 3 immune phenotypes associated with ME/CFS, and future work may explore the sensitivity of these for diagnosis or clinical sub-typing.

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

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

Overall, the researchers central conclusion is that the cerebrospinal fluid of people with ME/CFS exhibits a disturbed immune signature consistent with immune activation in the central nervous system. As Prof Mady Hornig explains, “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”, and she suggests that they may contribute to symptoms in both the peripheral parts of the body and the brain, from muscle weakness to brain fog.

Abstract
Title: 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.

Further reading
Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome. Hornig, et al. Molecular Psychiatry, 2015 March 31 – link
Study provides insights into basis for cognitive dysfunction. News Medical 2015, March 31 – link
Scientists find clues into cognitive dysfunction in chronic fatigue syndrome. Medical Xpress   2015, March 31 – link

Illustration credit
The cerebrospinal fluid (CSF). OpenStax CollegeAnatomy & Physiology, Connexions Web site