From the Scandinavian Journal of Immunology, 18 September 2015 [Epub ahead of print].
Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis.
Huth TK(1,2), Brenu EW(1,2), Ramos S(1,2), Nguyen T(1,2), Broadley S(3,4), Staines D(1,2), Marshall-Gradisnik S(1,2).
1) National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Southport, QLD, 4222, Australia.
2) School of Medical Science, Griffith University, Southport, QLD, 4222, Australia.
3) School of Medicine, Griffith University, Southport, QLD, 4222, Australia.
4) Gold Coast University Hospital, Southport, QLD, 4222, Australia.
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and Multiple Sclerosis (MS) patients suffer from debilitating fatigue which is not alleviated by rest. In addition to the fatigue=related symptoms suffered by CFS/ME and MS patients, dysfunction of the immune system and in particular, reduced Natural Killer (NK) cell cytotoxic activity has also been reported in CFS/ME and MS.
The purpose of this pilot study was to compare NK cellular mechanisms in CFS/ME and MS patients to investigate potential dysfunctions in the NK cell activity pathway. Flow cytometry protocols assessed CD56dim CD16+ and CD56bright CD16+/- NK cell expression of adhesion molecules, NK activating and inhibiting receptors, NK cell maturation and lytic proteins.
All participants in this study were female and included 14 CFS/ME patients, 9 MS patients and 19 non-fatigued controls. The patient groups and the non-fatigued controls were not taking any immunosuppressive or immune enhancing medications. In the MS cohort, KIR2DL5 was significantly increased on CD56bright CD16+/- NK cells and expression of CD94 was significantly increased on CD56dim CD16+ NK cells in comparison to the controls. Co-expression of CD57 and perforin was significantly increased on CD56dim CD16+ NK cells from CFS/ME patients compared to the MS and non-fatigued control participants.
The results from this pilot study suggest that NK cells from CFS/ME and MS patients may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway.
From the Journal of Drug Research and Development, 8 August 2015.
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): Characteristics of Responders to Rintatolimod
David R Strayer(1), Bruce C Stouch(2), Staci R Stevens(3), Lucinda Bateman(4), Charles W Lapp(5), Daniel L Peterson(6), William A Carter(1), William M Mitchell(7*).
1) Hemispherx Biopharma, Inc., Philadelphia, Pennsylvania, United States of America
2) BCS Statistical Solutions LLC, Philadelphia, Pennsylvania, United States of America
3) Workwell Foundation, Ripon, California, United States of America
4) Fatigue Consultation Clinic, Salt Lake City, Utah, United States of America
5) Hunter-Hopkins Center, Charlotte, North Carolina, United States of America
6) Sierra Internal Medicine Associates, Incline Village, Nevada, United States of America
7) Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
*Corresponding author: William M. Mitchell, Department of Pathology, Microbiology & Immunology, Vanderbilt University, Nashville, TN 37205, USA, Tel: 615-322-3238; E-mail: firstname.lastname@example.org
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disease of unknown pathogenesis consisting of a variety of flu-like symptoms including severe fatigue. Initial analysis of the use of rintatolimod (Poly I: Poly C12U), a selective TLR3 agonist, in a Phase III, double-blind, randomised, placebo-controlled trial of CFS/ME demonstrated statistical significance (p<0.05) in the reduction of fatigue as measured by exercise tolerance (ET) as the primary endpoint using a modified Bruce protocol with reduced physical exertion in patients with severe CFS/ME as defined by a Karnofsky performance score (KPS) of 40-60. METHODS AND FINDINGS In order to better identify responders to rintatolimod, primary and secondary endpoints have been reexamined post hoc as a function of a pre-specified study baseline ET duration >9 minutes. Analysis of improvement in exercise performance at the ≥ 25% and ≥ 50% levels using ET at 40 weeks compared to baseline was performed for the intent-to-treat (ITT) population (n=208) using the pre-specified baseline exercise stratum (baseline ET duration >9 minutes).
For this subset of patients (n=126), 33% (n=20), and 12% (n=8) of rintatolimod vs. placebo patients, respectively, improved ET duration by ≥ 25% (p=0.004) while 23% (n=14) compared to 4.5% (n=3) of rintatolimod vs. placebo patients, respectively improved ET duration by ≥ 50% (p=0.003). This corresponds to increases of ≥ 186 and ≥ 37 seconds for patients receiving rintatolimod, respectively, at ≥ 25% and ≥ 50% improvement responses. A frequency distribution analysis of ≥ 25% improvement, <25% change, and ≥ 25% deterioration in ET from baseline at 40 weeks for the baseline >9 minutes cohort showed net improvement to be 18.3% for the rintatolimod cohort vs. 4.6% deterioration for placebo (p=0.015). A continuous responder analysis using 5% increments from ≥ 25% to ≥ 50% provided a robust clinical enhancement in ET effect in the rintatolimod cohorts as compared to
placebo. The KPS and Vitality (SF-36 subscale) quality of life secondary endpoints demonstrated similar clinically significant improvements for the rintatolimod cohort as a function of the same ET dichotomization. Rintatolimod was generally well-tolerated in this CFS/ME population.
Using a modified Bruce ET protocol with reduced physical exertion allowed clear identification of patient responders to rintatolimod with severe CFS/ME syndrome. Rintatolimod produced significant enhancement in ET and quality of life indicators in patients able to complete >9 minutes in a modified Bruce ET test. Rintatolimod also reduced deterioration in ET compared to placebo in patients with the poorest initial ET. Exercise endurance >9 minutes in a Bruce protocol modified for patients with CFS/ME provides a method to identify patients most likely to respond to rintatolimod.
From the American Journal of Occupational Therapy, September 2015.
Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial
Daphne Kos; Inge van Eupen; Jill Meirte; Deborah Van Cauwenbergh; Greta Moorkens; Mira Meeus; Jo Nijs
Daphne Kos, PhD, OT, is Assistant Professor, Department of Rehabilitation Sciences, Neuromotor Research Group, KU Leuven–University of Leuven, Belgium; Lecturer, Division of Occupational Therapy, Department of Health and Social Care, Artesis Plantijn University College, Antwerp, Belgium; and Member, Pain in Motion Research Group, Brussels, Belgium; email@example.com
Inge van Eupen, OT, is Lecturer, Division of Occupational Therapy, Department of Health and Social Care, Artesis Plantijn University College, Antwerp, Belgium
Jill Meirte, PT, is PhD Researcher, Faculty of Medicine and Health Sciences, Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Antwerp, Belgium. At the time of the study, she was Lecturer, Artesis Plantijn University College, Antwerp, Belgium
Deborah Van Cauwenbergh, PT, is PhD Researcher, Faculty of Medicine and Health Sciences, Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Antwerp, Belgium. At the time of the study, she was Lecturer, Artesis Plantijn University College, Antwerp, Belgium
Greta Moorkens, PhD, MD, is Associate Professor, Department of General Internal Medicine of University of Antwerp, Belgium; and Warrant-Manager, University Hospital, Antwerp, Belgium
Mira Meeus, PhD, PT, is Associate Professor, Faculty of Medicine and Health Sciences, Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Belgium; Associate Professor, Faculty of Medicine and Health Sciences, Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Ghent, Belgium; and Member, Pain in Motion Research Group, Brussels, Belgium. At the time of the study, she was Lecturer, Artesis Plantijn University College, Antwerp, Belgium
Jo Nijs, PhD, PT, is Associate Professor, Departments of Human Physiology and Physiotherapy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit, Brussels, Belgium; Physiotherapist, Department of Physical Medicine and Physiotherapy, University Hospital, Brussels, Belgium; and Member, Pain in Motion Research Group, Brussels, Belgium. At the time of the study, he was Lecturer, Artesis Plantijn University College, Antwerp, Belgium.
The objective of this study was to evaluate the effectiveness of an activity pacing self-management (APSM) intervention in improving performance of daily life activities in women with chronic fatigue syndrome (CFS).
A total of 33 women with CFS (age 41.1 ± 11.2 yr) were randomly allocated to APSM (experimental group; n = 16) or relaxation (control group; n = 17). Main outcome measures included the Canadian Occupational Performance Measure (COPM; primary) and Checklist Individual Strength (CIS).
COPM scores changed significantly over time in both groups (p = .03). The change in Satisfaction scores showed a significant difference in favor only of APSM (effect size = 0.74 [0.11, 1.4]). CIS scores decreased significantly in the experimental group only (p < .01). CONCLUSION APSM was found to be feasible and effective in optimizing participation in desired daily life activities in women with CFS. Replication in a larger sample with long-term follow-up is required.