From Human Immunology, 28 September 2015. [Epub ahead of print].
Frequent IgG subclass and mannose binding lectin deficiency in patients with Chronic Fatigue Syndrome.
Guenther S(1), Loebel M(1), Mooslechner AA(1), Knops M(2), Hanitsch LG(1), Grabowski P(1), Wittke K(1), Meisel C(3), Unterwalder N(3), Volk HD(4), Scheibenbogen C(5).
1) Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
2) Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
3) Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany; Labor Berlin GmbH, Immunology Department, Charité Universitätsmedizin Berlin, Berlin, Germany.
4)Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
5)Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany. Electronic address: carmen.scheibenbogen@charite.de.
Abstract
Chronic fatigue syndrome (CFS) is a severe disease characterized by various symptoms of immune dysfunction. CFS onset is typically with an infection and many patients suffer from frequently recurrent viral or bacterial infections.
Immunoglobulin and mannose binding lectin (MBL) deficiency are frequent causes for increased susceptibility to infections.
In this study we retrospectively analysed 300 patients with CFS for immunoglobulin and MBL levels, and B-cell subset frequencies. 25% of the CFS patients had decreased serum levels of at least one antibody class or subclass with IgG3 and IgG4 subclass deficiencies as most common phenotypes.
However, we found elevated immunoglobulin levels with an excess of IgM and IgG2 in particular in another 25% of patients. No major alteration in numbers of B cells and
B-cell subsets was seen. Deficiency of MBL was found in 15% of the CFS patients in contrast to 6% in a historical control group.
In a 2nd cohort of 168 patients similar frequencies of IgG subclass and MBL deficiency were found. Thus, humoral immune defects are frequent in CFS patients and are associated with infections of the respiratory tract.
From Pain Physician, September-October 2015.
Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter.
Ickmans K(1), Meeus M(2), De Kooning M(3), Lambrecht L(4), Pattyn N(5), Nijs J(6).
1) Pain in Motion Research Group (www.paininmotion.be).
2,1) Pain in Motion Research Group (www.paininmotion.be); Rehabilitation Sciences and Physiotherapy, Faculty of Medicine & Health Sciences, Ghent University, Ghent, Belgium; Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium.
3) Pain in Motion Research Group (www.paininmotion.be); Department of Human Physiology and Physiotherapy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium; Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium; Department of Neurology, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
4) Private practice for internal medicine, Ghent, Belgium.
5) Department of Human Physiology and Physiotherapy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium; VIPER Research Unit, Royal Military Academy, Brussels, Belgium.
6) Pain in Motion Research Group (www.paininmotion.be); Department of Human Physiology and Physiotherapy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium; Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium;
Abstract
BACKGROUND
In addition to the frequently reported pain complaints, performance-based cognitive capabilities in patients with chronic fatigue syndrome (CFS) with and without comorbid fibromyalgia (FM) are significantly worse than those of healthy controls. In various chronic pain populations, cognitive impairments are known to be related to pain severity. However, to the best of our knowledge, the association between cognitive performance and experimental pain measurements has never been examined in CFS patients.
OBJECTIVES
This study aimed to examine the association between cognitive performance and self-reported as well as experimental pain measurements in CFS patients with and without FM.
STUDY DESIGN
Observational study.
SETTING
The present study took place at the Vrije Universiteit Brussel and the University of Antwerp.
METHODS
Forty-eight (18 CFS-only and 30 CFS+FM) patients and 30 healthy controls were studied. Participants first completed 3 performance-based cognitive tests designed to assess selective and sustained attention, cognitive inhibition, and working memory capacity. Seven days later, experimental pain measurements (pressure pain thresholds [PPT], temporal summation [TS], and conditioned pain modulation [CPM]) took place and participants were asked to fill out 3 questionnaires to assess self-reported pain, fatigue, and depressive symptoms.
RESULTS
In the CFS+FM group, the capacity of pain inhibition was significantly associated with cognitive inhibition. Self-reported pain was significantly associated with simple reaction time in CFS-only patients. The CFS+FM but not the CFS-only group showed a significantly
lower PPT and enhanced TS compared with controls.
LIMITATIONS
The cross-sectional nature of this study does not allow for inferences of causation.
CONCLUSIONS
The results underline disease heterogeneity in CFS by indicating that a measure of endogenous pain inhibition might be a significant predictor of cognitive functioning in CFS patients with FM, while self-reported pain appears more appropriate to predict cognitive functioning in CFS patients without FM.
From Trials, 5 October 2015.
Cytokine inhibition in chronic fatigue syndrome patients: study protocol for a randomized controlled trial.
Roerink ME(1), Knoop H(2), Bredie SJ(3), Heijnen M(4), Joosten LA(5), Netea MG(6), Dinarello CA(7), van der Meer JW(8).
1) Department of Internal Medicine, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. Megan.Roerink@radboudumc.nl.
2) Expert Centre Chronic Fatigue, Radboud University Medical Center, Nijmegen, The Netherlands. Hans.Knoop@radboudumc.nl.
3) Department of Internal Medicine, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. Bas.Bredie@radboudumc.nl.
4) Department of Internal Medicine, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. Michael.Heijnen@radboudumc.nl.
5) Department of Internal Medicine, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. Leo.Joosten@radboudumc.nl.
6) Department of Internal Medicine, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. Mihai.Netea@radboudumc.nl.
7) Department of Internal Medicine, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. Dinarello@ucdenever.edu.
8) Department of Internal Medicine, Radboud University Medical Center, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. Jos.vanderMeer@radboudumc.nl.
Abstract
BACKGROUND
Chronic fatigue syndrome (CFS) is a medically unexplained syndrome for which no somatic or pharmacological treatment has been proven effective. Dysfunction of the cytokine network has been suspected to play a role in the pathophysiology of CFS. The disturbances of the cytokine network detected in CFS patients are highly variable, in part due to the lack of adequate controls in many studies. Furthermore, all studies have been performed on peripheral venous blood of patients. As cytokines mainly act in tissues, for example, the brain, the information that can be derived from peripheral blood cells is limited. The information regarding the possible role of cytokines in the pathophysiology could come from intervention studies in which the activities of relevant cytokines are reduced, for example, reducing interleukin-1, interleukin-6 or tumor necrosis factor. In this study, the clinical usefulness of anakinra, an IL-1 antagonist, will be assessed in patients with CFS.
METHODS/DESIGN
A randomized placebo-controlled, double-blind trial will be conducted. Fifty adult female patients meeting the Centers for Disease Control (CDC) criteria for CFS and without psychiatric co-morbidity will be included. After inclusion, patients will be randomized between treatment with anakinra (recombinant human interleukin-1 receptor antagonist) or placebo. Each group will be treated for 4 weeks. Outcome measures will be assessed at baseline, after 4 weeks of intervention, and 6 months after baseline assessment. The primary outcome measure will be fatigue severity at 4 weeks, measured with the validated Checklist of Individual Strength (CIS). Secondary outcome measures are functional impairment, physical and social functioning, psychological distress, pain severity, presence of accompanying symptoms, and cytokine and cortisol concentrations.
DISCUSSION
This is the first randomized placebo-controlled trial that will evaluate the effect of interference with IL-1 on the experience of fatigue in patients with CFS. The results of this study may expand treatment options for patients with CFS, for whom graded exercise therapy and cognitive behavioral therapy are the only evidence-based interventions that exist at this moment.
TRIAL REGISTRATION
Clinicaltrials.gov: NCT02108210 . Clinicaltrials.gov registration date: 8 April 2014. EudraCT: 2013-005466-19.