TGI Friday! Our weekly round-up of recently published research abstracts | 13 December 2013

December 13, 2013

From PLosOne, 28 November 2013.

Research Article

Epitopes of Microbial and Human Heat Shock Protein 60 and Their Recognition in Myalgic Encephalomyelitis

Amal Elfaitouri, Björn Herrmann, Agnes Bölin-Wiener, Yilin Wang, Jonas Blomberg
Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Carl-Gerhard Gottfries, Olof Zachrisson
Gottfries Clinic AB, Mölndal, Sweden
Rϋdiger Pipkorn
Deutsches Krebsforschungszentrum, Heidelberg, Germany
Lars Rönnblom
Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
* E-mail:


Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen.

The anti-HSP60 humoral (IgG and IgM) immune response was studied in 69 ME patients and 76 blood donors (BD) (the Training set) with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding.

A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

From Psychoneuroendocrinology, February 2014.

An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity

T.M. Dantoft(a), J. Elberling(a), S. Brix(b), P.B. Szecsi(c), S. Vesterhauge(d), S. Skovbjerg(a)

a) The Danish Research Centre for Chemical Sensitivities, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Gentofte, Denmark
b) Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark
c) Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Gentofte, Denmark
d) Aleris-Hamlet, Private Hospital, Copenhagen, Denmark



Multiple chemical sensitivity (MCS) is a medically unexplained condition characterized by reports of recurrent unspecific symptoms attributed to exposure to low levels of common volatile chemicals. The etiology of MCS is poorly understood, but dysregulation of the immune system has been proposed as part of the pathophysiology.


To compare plasma levels of cytokines in Danish MCS individuals with a healthy, sex- and age-matched control group.


Blood samples were obtained from 150 un-exposed MCS individuals and from 148 age- and sex-matched healthy controls. Plasma concentrations of 14 cytokines, chemokines and growth and allergen-specific IgE were measured. All participants completed a questionnaire including questions on MCS, psychological distress, morbidities and medication use at the time of the study.


Plasma levels of interleukin-1β, -2, -4, and -6 were significantly (P <0.001) increased in the MCS group compared with controls, tumor necrosis factor-α was borderline significantly (p = 0.05) increased and interleukin-13 was significantly decreased.CONCLUSIONMCS individuals displayed a distinct systemic immune mediator profile with increased levels of pro-inflammatory cytokines and interleukin-2 and inverse regulation of Th2 associated cytokines interleukin-4 and interleukin-13 suggestive of low-grade systemic inflammation, along with a deviating Th2-associated cytokine response not involving IgE-mediated mechanisms.

From Evidence-Based Complementary and Alternative Medicine, accepted 1 October 2013.

Review Article

Classification and Clinical Diagnosis of Fibromyalgia Syndrome: Recommendations of Recent Evidence-Based Interdisciplinary Guidelines

Mary-Ann Fitzcharles(1), Yoram Shir(2), Jacob N. Ablin(3), Dan Buskila(4), Howard Amital(5), Peter Henningsen(6) and Winfried Häuser(6,7).
1) Division of Rheumatology, McGill University Health Centre, Alan Edwards Pain Management Unit, McGill University Health Centre, Canada H3G 1A4
2) Alan Edwards Pain Management Unit, McGill University Health Centre, Canada H3G 1A4
3) Department of Rheumatology, Tel Aviv Sourasky Medical Center, 64329 Tel Aviv, Israel
4) Department of Medicine, H. Soroka Medical Center, 84101 Beer-Sheva, Israel
5) Department of Medicine “B” and Centre for Autoimmune Diseases, Sheba Medical Centre, 52621 Tel Hashomer, Israel
6) Department Internal Medicine I, Klinikum Saarbrücken, Winterberg 1, 66119 Saarbrücken, Germany
7) Department of Psychosomatic Medicine and Psychotherapy, Technische Universität München, 81865 München, Germany



Fibromyalgia syndrome (FMS),characterized by subjective complaints without physical or biomarker abnormality, courts controversy. Recommendations in recent guidelines addressing classification and diagnosis were examined for consistencies or differences.


Systematic searches from January 2008 to February 2013 of the US-American National Guideline Clearing House, the Scottish Intercollegiate Guidelines Network, Guidelines International Network, and Medline for evidence-based guidelines for the management of FMS were conducted.


Three evidence-based interdisciplinary guidelines, independently developed in Canada, Germany, and Israel, recommended that FMS can be clinically diagnosed by a typical cluster of symptoms following a defined evaluation including history, physical examination, and selected laboratory tests, to exclude another somatic disease. Specialist referral is only recommended when some other physical or mental illness is reasonably suspected. The diagnosis can be based on the (modified) preliminary American College of Rheumatology (ACR) 2010 diagnostic criteria.


Guidelines from three continents showed remarkable consistency regarding the clinical concept of FMS, acknowledging that FMS is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms, not explained by another somatic disease. While FMS remains an integral part of rheumatology, it is not an exclusive rheumatic condition and spans a broad range of medical disciplines.

From Journal of Sex & Marital Therapy, epublished 25 November 2013.

The impact of fatigue and fibromyalgia on sexual dysfunction in women with Chronic Fatigue Syndrome

Alicia Blazquez, Eva Ruiz, Luisa Aliste, Ana Garcia-Quintana & Jose Alegre
Unity of CFS and Fibromyalgia, Vall Hebron Hospital, Internal Medicine, Barcelona, Spain


Sexual dysfunction in patients with chronic fatigue syndrome (CFS) is attracting growing interest but has been analyzed by few studies to date. For this reason we evaluate sexual dysfunction in women with CFS (GRISS) and explore correlations with fatigue and other symptoms. Sexual dysfunction was greater in CFS patients (n=615) with a higher number of cognitive, neurological, and neurovegetative symptoms, concomitant fibromyalgia, Sjogren's syndrome, or myofascial pain syndrome, and more intense fatigue (P<0.05).

From Molecular Biomarkers & Diagnosis, 2013, 4:3

Immune Abnormalities in Patients Meeting New Diagnostic Criteria for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Brenu EW(1,2*), Johnston S(1,2), Hardcastle SL(1,2), Huth TK1,2, Fuller K(1,2), Ramos SB(1,2), Staines DR(2,3) and Marshall-Gradisnik SM(1,2)
1) School of Medical Science, Griffith University, Gold Coast, Queensland, Australia
2) The National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, Queensland, Australia 3) Queensland Health, Gold Coast Public Health Unit, Robina, Gold Coast, Queensland, Australia



Immunological abnormalities have been identified in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients fulfilling the 1994 Centers for Disease Control diagnostic criteria. Significant developments have been made to diagnostic criteria, but potential immunological markers have not been assessed in patients fulfilling these latest clinical requirements. Therefore, this study evaluated immunological parameters in patients that also fulfill the latest diagnostic criteria available known as the International Consensus Criteria.


The Immunological investigations including Natural Killer cell activity and phenotyping studies for dendritic cells, neutrophils, B cells and regulatory T cells were performed on whole blood samples collected from all participants using flow cytometric protocols. The physical functioning of all participants was also evaluated using scores from the Short Form Health Survey, and the World Health Organization Disability Adjustment Schedule. Results were compared according 1994 Centers of Disease Control and Prevention defined patients, and International Consensus Criteria defined patients, and healthy controls.

RESULTS Natural killer cell activity was consistently and significantly decreased, and regulatory T cells were significantly increased in both patient groups compared to healthy controls. Differences were found in human neutraphil antigens and expression of natural killer cell receptors between patient groups. Highly significant correlations were also found between physical status and some immune parameters in International Consensus Criteria defined patients.


This preliminary investigation on different diagnostic criteria suggests that the International Consensus Criteria may be more effective a detecting salient differences in the immune system.

From the Journal of the Royal Society of Medicine, 2 December 2013.

Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study

Nicholas Higgins(1), John Pickard(2), and Andrew Lever(3)
1) Department of Radiology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
2) Academic Department of Neurosurgery, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
3) Department of Infectious diseases, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
Corresponding author:
Nicholas Higgins. Email:



Unsuspected idiopathic intracranial hypertension (IIH) is found in a significant minority of patients attending clinics with named headache syndromes, if it is specifically sought out. Chronic fatigue syndrome is frequently associated with headache. Could the same be true of chronic fatigue? Moreover, there are striking similarities between the two conditions. Could they be related? Attempting to answer these questions, we describe the results of a change in clinical practice aimed at capturing patients with chronic fatigue who might have IIH.




Hospital outpatient and radiology departments.


Patients attending a specialist clinic with chronic fatigue syndrome and headache who had lumbar puncture to exclude raised intracranial pressure.


Intracranial pressure measured at lumbar puncture and the effect on headache of cerebrospinal fluid drainage.


Mean cerebrospinal fluid pressure was 19cm H2O (range 12–41cm H2O). Four patients fulfilled the criteria for IIH. Thirteen others did not have pressures high enough to diagnose IIH but still reported an improvement in headache after drainage of cerebrospinal fluid. Some patients also volunteered an improvement in other symptoms, including fatigue. No patient had any clinical signs of raised intracranial pressure.


An unknown, but possibly substantial, minority of patients with chronic fatigue syndrome may actually have IIH. An unknown, but much larger, proportion of patients with chronic fatigue syndrome do not have IIH by current criteria but respond to lumbar puncture in the same way as patients who do. This suggests that the two conditions may be related.

From the European Journal of Clinical Investigation, 11 November 2013 (epublished ahead of print).

Recovery of upper limb muscle function in chronic fatigue syndrome with and without fibromyalgia.

Kelly Ickmans(1,2,3), Mira Meeus(2,4,5), Margot De Kooning(1,3,6), Luc Lambrecht(7), Jo Nijs(1,3,*)
1) Pain in Motion Research Group, Department of Human Physiology and Physiotherapy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussel, Belgium
2) Pain in Motion Research Group, Division of Musculoskeletal Physiotherapy, Department of Health Care Sciences, Artesis University College Antwerp, Antwerp, Belgium
3) Pain in Motion Research Group, Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium
4) Rehabilitation Sciences and Physiotherapy, Faculty of Medicine & Health Sciences, Ghent University, Gent, Belgium
5) Pain in Motion Research Group, Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium
6) Department of Neurology, Faculty of Medicine, University of Antwerp (UA), Antwerp, Belgium
7) Private practice for internal medicine, Ghent, Belgium
*Correspondence to: Jo Nijs, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Medical Campus Jette, Building F-Kine, Laarbeeklaan 103, BE-1090 Brussels, Belgium. Tel.: +3224774489; fax +3226292876; e-mail



Chronic fatigue syndrome (CFS) patients frequently complain of muscle fatigue and abnormally slow recovery, especially of the upper limb muscles during and after activities of daily living. Furthermore, disease heterogeneity has not yet been studied in relation to recovery of muscle function in CFS. Here, we examine
recovery of upper limb muscle function from a fatiguing exercise in CFS patients with (CFS+FM) and without (CFS-only) comorbid fibromyalgia and compare their results with a matched inactive control group.


In this case-control study, 18 CFS-only patients, 30 CFS+FM patients and 30 healthy inactive controls performed a fatiguing upper limb exercise test with subsequent recovery measures.


There was no significant difference among the three groups for maximal handgrip strength of the non-dominant hand. A significant worse recovery of upper limb muscle function was found in the CFS+FM, but not in de CFS-only group compared with the controls (P < 0·05).CONCLUSIONSThis study reveals, for the first time, delayed recovery of upper limb muscle function in CFS+FM, but not in CFS-only patients. The results underline that CFS is a heterogeneous disorder suggesting that reducing the heterogeneity of the disorder in future research is important to make progress towards a better understanding and uncovering of mechanisms regarding the nature of divers impairments in these patients.

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