TGI Friday! Our regular round-up of recently published research abstracts | 11 December 2015

December 11, 2015

From Cytokine. 2015 Nov 23;78:27-36. doi: 10.1016/j.cyto.2015.11.018. [Epub ahead of print].

Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome.

Landi A(1), Broadhurst D(2), Vernon SD(3), Tyrrell DL(4), Houghton M(5).
1) Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, Canada. Electronic address:
2) Department of Medicine, Katz Group Centre for Pharmacy & Health, University of Alberta, Edmonton, AB T6G 2E1, Canada.
3) Bateman Horne Center, 1002 E. South Temple, Suite 408, Salt Lake City, UT 84102, USA.
4) Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, Canada.
5) Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, Canada. Electronic address:


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 3years.

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-γ (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.

From BMC Nursing (open access), 28 November 2015.

Fatigue in adults with post-infectious fatigue syndrome: a qualitative content analysis

Eva Stormorken(1*), Leonard A. Jason(2) and Marit Kirkevold(1)
Corresponding author: Eva Stormorken
1) Department of Nursing Science, Institute of Health and Society, University of Oslo, Blindern 0318, Oslo, Norway
2) Center for Community Research, DePaul University, 990 W. Fullerton Ave, Suite 3100, Chicago 60614, Illinois, USA



Fatigue is a major problem among individuals with post-infectious fatigue syndrome (PIFS), also known as chronic fatigue syndrome or myalgic encephalomyelitis. It is a complex phenomenon that varies across illnesses. From a nursing perspective, knowledge and understanding of fatigue in this illness is limited. Nurses lack confidence in caring for these patients and devalue their professional role. The aim of this study was to explore in-depth the experiences of fatigue among individuals with PIFS. A detailed description of the phenomenon of fatigue is presented. Increased knowledge would likely contribute to more confident nurses and improved nursing care.


A qualitative study with open interviews was employed. In-depth interviews with patients were fully transcribed and underwent a qualitative content analysis. A maximum variation sample of 26 affected adults between 26–59 years old was recruited from a population diagnosed at a fatigue outpatient clinic.


The fatigue was a post-exertional, multidimensional, fluctuating phenomenon with varying degrees of severity and several distinct characteristics and was accompanied by concomitant symptoms. Fatigue was perceived to be an all-pervasive complex experience that substantially reduced the ability to function personally or professionally. A range of trigger mechanisms evoked or worsened the fatigue, but the affected were not always aware of what triggered it. There was an excessive increase in fatigue in response to even minor activities. An increase in fatigue resulted in the exacerbation of other concomitant symptoms. The term fatigue does not capture the participants’ experiences, which are accompanied by a considerable symptom burden that contributes to the illness experience and the severe disability.


Although some aspects of the fatigue experience have been reported previously, more were added in our study, such as the dimension of awakening fatigue and the characteristic beyond time, when time passes unnoticed. We also identified trigger mechanisms such as emotional, neurological, social, financial, and pressure on oneself or from others. This in-depth exploration of fatigue in PIFS provides an overview of the dimensions, characteristics, and trigger mechanisms of fatigue, thus making better clinical observations, early recognition, improved communication with patients and more appropriate nursing interventions possible.

From InnoVait (education and inspiration for general practice), December 2015.

Managing medically unexplained symptoms

Dr David Roberts
Ninewells Hospital and Medical School, Dundee


Medically unexplained symptoms (MUS) are the presenting symptoms in a significant number of medical consultations in the UK. In many cases, the outcome is unsatisfactory for both the doctor and the patient. This may be partly due to the ongoing nature of the patient’s complaint and dissatisfaction due to lack of closure at the end of the consultation.

The relationship between the doctor and the patient is of paramount importance, since a cure may not be possible and understanding of the patient’s condition may be limited. Good communication skills are needed to improve the effectiveness of consultations in cases where other medical interventions are of limited value.

This article reviews the current understanding of MUS. Aspects of the medical consultation are analysed and strategies for patient management and future care are made.

From Clinical and Experimental Immunology, epublished before print on 8 December 2015.

Dr Charles Shepherd comments: “This new research on B-cell status in ME/CFS may have some relevance to a clinical trial of Rituximab that will hopefully take place here in the UK.”

Extended B-cell phenotype in patients with Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: A cross-sectional study

Fane Mensah(1), Amolak Bansal(2), Saul Berkovitz(3), Arti Sharma(1), Venkat Reddy(1), Maria J. Leandro(1) and Geraldine Cambridge(1,*)
1) Department of Rheumatology Research, Division of Medicine, University College of London, London, United Kingdom
2) Department of Immunology, Epsom and St Helier University Hospitals NHS Trust, London, United Kingdom
3) Department of Neurology, Royal London Hospital Of Integrated Medicine, London, United Kingdom
* Corresponding Author: Geraldine Cambridge, PhD, Department of Rheumatology Research, Division of Medicine, University College London, Rayne Building, 5 University Street, London WC1E 6JF, United Kingdom.


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous condition of unknown etiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months.

Recently, two clinical trials of B-cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B-cells has therefore been proposed. Studies of the relative percentages of B-cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC).

In order to explore whether more subtle alterations in B-cell subsets related to B-cell
differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19+ B-cells. The panel utilized IgD, CD27 and CD38 (classical B-cell subsets) together with additional markers.

A total of 38 patients fulfilling Canadian, Centre for Disease Control, and Fukuda ME/CFS criteria and 32 age/sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (p<0.01) and expression (MFI; p=0.03) of CD24 on total B-cells, confined to IgD+ subsets.Within memory subsets, a higher frequency of CD21+ CD38- B-cells (>20%) was associated with the presence of ME/CFS (Odds ratio: 3.47 (1.15-10.46); p=0.03) compared with HC and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B-cell phenotype in patients with ME/CFS. These may reflect altered B-cell function and if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab-therapy.

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