From Fatigue: Biomedicine, Health & Behavior, published online 28 April 2016 (open access).
The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem
Jonathan C.W. Edwards(a), Simon McGrath(b), Adrian Baldwin©, Mark Livingstone(d) & Andrew Kewley(e)
a) Division of Medicine, University College London, London, UK
b) Monmouth, UK
c) Bristol, UK
d) Cognac, France
e) Adelaide, Australia
The Phoenix Rising forum provided facilities for these authors to collaborate on this editorial.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is comparable to multiple sclerosis, diabetes or rheumatoid arthritis in prevalence (∼0.2% to 1%), long-term disability, and quality of life, yet the scale of biomedical research and funding has been pitifully limited, as the recent National Institutes of Health (NIH) and Institute of Medicine reports highlight.
Recently in the USA, NIH Director Francis Collins has stated that the NIH will be ramping up its efforts and levels of funding for ME/CFS, which we hope will greatly increase the interest in, and resources for researching this illness. Despite scant funding to date, researchers in the field have generated promising leads that throw light on this previously baffling illness. We suggest the key elements of a concerted research programme and call on the wider biomedical research community to actively target this condition.
From The FASEB Journal, April 2016.
Telomere Length Analysis in Chronic Fatigue Syndrome
E R Unger, J Murray, LP Oakley, JM Lin and MS Rajeevan
Centers for Disease Control and Prevention, Atlanta, GA
Chronic fatigue syndrome (CFS) is a severely disabling condition associated with multi-system symptoms including marked post-exertional malaise, fatigue, pain, unrefreshing sleep and cognitive impairment. The symptoms and risk factors share features with accelerating aging. Aging and a variety of metabolic, inflammatory, infectious and neoplastic conditions have been associated with accelerated telomere attrition. This analysis was performed to evaluate whether CFS shares this association.
DNA was isolated from 705 PAXgene whole blood samples from 751 participants in the 2007–09 follow-up of the Georgia CFS Surveillance study who completed the clinical evaluation used to identify exclusionary medical and psychiatric conditions that could explain fatigue.
Using the 1994 CFS Research Case Definition with questionnaire-based subscale thresholds for fatigue, function and symptoms, participants were classified as: 1) CFS if all criteria met (n=71); 2) CFS-X if CFS with exclusionary conditions (n=78); 3) Insufficient Symptoms/Fatigue (ISF) if only some criteria met, regardless of exclusionary conditions (n=340); 4) Non-Fatigued (NF) if no criteria met and no exclusionary conditions (n=212;47 NF participants with exclusions were not included and 3 could not be classified). Relative telomere length was measured using real-time PCR.
Telomere specific primers generate a signal proportional to total sum of the length of all telomeres in the sample (T). Telomere signal is normalized to signal from primers to single-copy gene (S). The T/S ratio is proportional to average telomere length per cell. T/S is expressed relative to reference DNA, assigned T/S of 1.0. Conversion of T/S to Southern blot hybridization determination of terminal restriction fragment telomere length in base pairs (bp) was based on data from 20 healthy volunteers tested by both methods.
Linear and logistic models were used to examine association between CFS, T/S ratio and covariates. Level of significance was set at p < 0.05. This analysis concerned 639 participants with telomere, classification and co-variate data: 77 CFS-X, 64 CFS, 302 ISF, and 196 NF. RESULTS Age (48.04 ± 0.38 years) did not differ across groups, but obesity, sex, race, education and income, significantly differed. T/S ratios ranged from 0.269 to 4.138. When comparing T/S ratios across groups, telomere lengths were significantly shorter in CFS and ISF than NF (CFS: 0.93±0.03, ISF: 0.94±0.02; NF: 1.09±0.04). These differences remained significant after adjusting for covariates (age, BMI, waist-hip-ratio, education, and sex). Based on adjusted group means, telomere length was shorter by 212, 593 and 508 bp in CFS-X, CFS and ISF compared to NF. As expected there was a significant negative correlation between telomere length and age in the study sample overall. NF subjects started with long telomeres but shortened at a faster rate (59 bp/year) than the rate of telomere shortening in CFS-X (25.4 bp/year), CFS (21.2 bp/year) and ISF (4.2 bp/year). CONCLUSIONS Our results indicate that CFS should be included in the list of conditions associated with telomere shortening. Further work is needed to evaluate if the shortening has functional significance in CFS. FOOTNOTES This abstract is from the Experimental Biology 2016 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
From Diagnostics, 22 April 2016 (open access).
The Relationship between Age and Illness Duration in Chronic Fatigue Syndrome
Elizabeth Kidd(1), Abigail Brown(1), Stephanie McManimen(1), Leonard A. Jason (1,*), Julia L. Newton(2) and Elin Bolle Strand(3)
1) Center for Community Research, DePaul University, 990 W Fullerton Avenue Suite 3100, Chicago, IL 60614, USA
2) Clinical Medicine, Newcastle University, Newcastle NE2 4HH, England.
3) Division of Medicine, Oslo University Hospital, 0450 Oslo, Norway, Norway.
* Correspondence: email@example.com
Chronic fatigue syndrome (CFS) is a debilitating illness, but it is unclear if patient age and illness duration might affect symptoms and functioning of patients.
In the current study, participants were categorized into four groups based upon age (under or over age 55) and illness duration (more or less than 10 years). The groups were compared on functioning and symptoms.
Findings indicated that those who were older with a longer illness duration had significantly higher levels of mental health functioning than those who were younger with a shorter or longer illness duration and the older group with a shorter illness duration.
The results suggest that older patients with an illness duration of over 10 years have significantly higher levels of mental health functioning than the three other groups.
For symptoms, the younger/longer illness duration group had significantly worse immune and autonomic domains than the older/longer illness group.
In addition, the younger patients with a longer illness duration displayed greater autonomic and immune symptoms in comparison to the older group with a longer illness duration. These findings suggest that both age and illness duration need to be considered when trying to understand the influence of these factors on patients.
From Applied Clinical Genetics, 31 March 2016.
Natural killer cells and single nucleotide polymorphisms of specific ion channels and receptor genes in myalgic encephalomyelitis/chronic fatigue syndrome
Sonya Marshall-Gradisni(1,2), Teilah Huth(1,2), Anu Chacko(1,2), Samantha Johnston(1,2), Pete Smith (2) and Donald Staines(2).
1) School of Medical Science, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia
2) National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia
Correspondence: Sonya Marshall-Gradisnik, firstname.lastname@example.org
The aim of this paper was to determine natural killer (NK) cytotoxic activity and if single nucleotide polymorphisms (SNPs) and genotypes in transient receptor potential (TRP) ion channels and acetylcholine receptors (AChRs) were present in isolated NK cells from previously identified myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients.
SUBJECTS AND METHODS
A total of 39 ME/CFS patients (51.69±2 years old) and 30 unfatigued controls (47.60±2.39 years old) were included in this study. Patients were defined according to the 1994 Centers for Disease Control and Prevention criteria. Flow cytometry protocols were used to examine NK cytotoxic activity. A total of 678 SNPs from isolated NK cells were examined for 21 mammalian TRP ion channel genes and for nine mammalian AChR genes via the Agena Bioscience iPlex Gold assay. SNP association and genotype was determined using analysis of variance and Plink software.
ME/CFS patients had a significant reduction in NK percentage lysis of target cells (17%±4.68%) compared with the unfatigued control group (31%±6.78%). Of the 678 SNPs examined, eleven SNPs for TRP ion channel genes (TRPC4, TRPC2, TRPM3, and TRPM8) were identified in the ME/CFS group. Five of these SNPs were associated with TRPM3, while the remainder were associated with TRPM8, TRPC2, and TRPC4 (P<0.05). Fourteen SNPs were associated with nicotinic and muscarinic AChR genes: six with CHRNA3, while the remainder were associated with CHRNA2, CHRNB4, CHRNA5, and CHRNE (P<0.05). There were sixteen genotypes identified from SNPs in TRP ion channels and AChRs for TRPM3 (n=5), TRPM8 (n=2), TRPC4 (n=3), TRPC2 (n=1), CHRNE (n=1), CHRNA2 (n=2), CHRNA3 (n=1), and CHRNB4 (n=1) (P<0.05). CONCLUSION We identified a number of SNPs and genotypes for TRP ion channels and AChRs from isolated NK cells in patients with ME/CFS, suggesting these SNPs and genotypes may be involved in changes in NK cell function and the development of ME/CFS pathology. These anomalies suggest a role for dysregulation of Ca2+ in AChR and TRP ion channel signaling in the pathomechanism of ME/CFS.
From Medicine and Science in Sports Exercise, published online 26 April 2016.
Graded vs Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome
Broadbent S1, Coutts R.
School of Health and Human Sciences, Southern Cross University, Lismore NSW, Australia
There is increasing evidence of immune system dysfunction in Chronic Fatigue Syndrome (CFS) but little is known of the regular exercise effects on immune cell parameters. This pilot study investigated the effects of graded and intermittent exercise on CD4 lymphocyte subset counts and activation compared to usual care.
24 CFS patients (50.2 ± 10 yr) were randomised to Graded exercise (GE), Intermittent exercise (IE) or usual care (UC) groups; 18 sedentary non-CFS participants (50.6 ± 10 yr) were controls (CTL) for blood and immunological comparisons.
Outcome measures were pre- and post-intervention flow cytometric analyses of circulating lymphocyte subset cell counts, expression of CD3, CD4, CD25 and CD134, full blood counts and V[Combining Dot Above]O2peak
Pre-intervention, CD3 cell counts and expression of CD4, CD25, CD134 and CD4CD25CD134 were significantly lower in GE, IE and UC compared to CTL (f < 0.05). Total lymphocyte concentration was significantly lower in GE and IE groups compared to CTL. There were significant post-intervention increases in (i) expression of CD4 and CD4CD25CD134 for GE and IE, but CD25 and CD134 for IE only; (ii) circulating counts of CD3 and CD4 for GE, and CD3, CD4, CD8, CD3CD4CD8, CD3CD16CD56, CD19 and CD45 for IE; (iii) neutrophil concentration for GE; (iv) V[Combining Dot Above]O2peak and elapsed test time for IE and GE, V[Combining Dot Above]Epeak for IE. CONCLUSIONS Twelve weeks of GE and IE training significantly improved CD4 lymphocyte activation and aerobic capacity without exacerbating CFS symptoms. IE may be a more effective exercise modality with regard to enhanced CD4 activation in CFS patients.