Research highlights:

• Abnormal cytokine/chemokine profile in ME/CFS associated with clinical symptoms.
• A cluster of IL-16, IL-7 and VEGF-A that may suggests neuro-inflammation as the pathogenesis mechanism in ME/CFS.
• Potential diagnostic biomarkers proven by vigorous mathematical/statistical analysis.

Abstract:

Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls.

Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3 years.

In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls.

We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients.

All three biomarkers were significantly correlated in a multivariate cluster analysis.

In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-y (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients.

Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced.

Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients.

To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients.

In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease.

This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes.

Further studies of other ME/CFS and overlapping disease cohorts are warranted in future.

1. Introduction

Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a complex and severely debilitating disease characterized by profound fatigue lasting for more than six months, post-exercise malaise, unrefreshing sleep, chronic pain, and cognitive dysfunction.

It is more common in middle-age women with an estimated prevalence of 0.8 million people in the USA and 0.4–1% in the world [1] and [2].

There is no laboratory test for diagnosis and no approved cure for the illness.

Diagnosis has been difficult, subjective and controversial leaving an urgent need for an objective laboratory-based diagnostic test for this very challenging illness.

Currently, the disease is diagnosed solely by subjective clinical symptoms [3] and evidence for an infectious etiology has been controversial [4], [5], [6], [7] and [8].

There is some evidence suggesting that the patients might suffer from a neuro-immune disorder [9] with neuroinflammation in the brain [10].

Alterations in the frequency and function of immune cells such as B cells and NK cells have been also reported [11] and [12].

Abnormalities in the concentrations of some circulating cytokines and chemokines have been previously reported [13], [14], [15], [16], [17] and [18] including three very recent studies of plasma and cerebrospinal fluid (CSF) samples from ME/CFS patients [19], [20]
and [21].

However, so far, there has been little confirmation of these abnormal analytes between different ME/CFS patient groups.

The objective of the current study was to measure the levels of various chemokines, cytokines and growth factors in the plasma of 100 ME/CFS patients from the USA along with 79 gender and age-matched controls to see if any consensus with previous studies
could be identified.

Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome, by Abdolamir Landia, David Broadhurst, Suzanne D. Vernon, D. Lorne J. Tyrrell, Michael Houghton, in Cytokine Vol 78, February 2016 pp27-36  [Available online 28 November 2015]

ME action: Study finds evidence of downregulated immune system in ME/CFS patients