From PLosOne (open access to full text), 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,
Carl-Gerhard Gottfries, Olof Zachrisson, Rϋdiger Pipkorn, Lars
Rönnblom, Jonas Blomberg * E-mail: jonas.blomberg@medsci.uu.se
Abstract
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, 26 November 2013 (E-published before print).
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
Abstract
BACKGROUND
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.
OBJECTIVE
To compare plasma levels of cytokines in Danish MCS individuals with a healthy, sex- and age-matched control group.
METHOD
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.
RESULTS
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 (open access), 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
Abstract
OBJECTIVES
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.
METHODS
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.
RESULTS
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.
DISCUSSION
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 Molecular Biomarkers & Diagnosis (open access), recent publication (date not known).
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
Abstract
BACKGROUND
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.
METHODS
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.
CONCLUSION
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.