TGI Friday! Our weekly round-up of recently published research abstracts | 29 May 2015

May 29, 2015

From the Journal of Translational Medicine, 20 May 2015 (e-published before print).

Submaximal exercise testing with near-infrared spectroscopy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients compared to healthy controls: a case-control study

Ruth R Miller(1), W Darlene Reid(2), Andre Mattman(3), Cristiane Yamabayashi(4), Theodore Steiner(5), Shoshana Parker(6), Jennifer Gardy(7), Patrick Tang(8), David M Patrick(9,10)
1) School of Population and Public Health, British Columbia Centre for Disease Control, University of British Columbia, 655 West 12th Avenue, Vancouver, BC, V5Z 4R4, Canada.
2) Department of Physical Therapy, University of Toronto, 160-500 University Avenue, Toronto, ON, M5G 1V7, Canada.
3) Adult Metabolic Disease Clinic, Vancouver General Hospital, Level 4, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.
4) Muscle Biophysics Laboratory, Department of Physical Therapy, University of British Columbia, 828 West 10th Avenue, Vancouver, BC, V5Z 3P1, Canada.
5) Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, V5Z 3J5, Canada.
6) Centre for Health Evaluation and Outcome Sciences, 588-1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
7) British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, BC, V5Z 4R4, Canada.
8) British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, BC, V5Z 4R4, Canada.
9 School of Population and Public Health, British Columbia Centre for Disease Control, University of British Columbia, 655 West 12th Avenue, Vancouver, BC, V5Z 4R4, Canada.
10) British Columbia Centre for Disease Control, 655 West 12th Avenue, Vancouver, BC, V5Z 4R4, Canada.



Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness. Symptoms include profound fatigue and distinctive post-exertional malaise (PEM). We asked whether a submaximal exercise test would prove useful for identifying different patterns of tissue oxygen utilization in individuals with ME/CFS versus healthy subjects. Such a test has potential to aid with ME/CFS diagnosis, or to characterize patients' illness.


A case-control study of 16 patients with ME/CFS compared to 16 healthy controls completing a 3-min handgrip protocol was performed. Response was measured using near-infrared spectroscopy, resulting in measurements of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) over wrist extensors and flexors. Changes in O2Hb (delta (d)O2Hb) and HHb (dHHb) absorbance between the first and last contraction were calculated, as were the force-time product of all contractions, measured as tension-time index (TTI), and ratings of perceived exertion (RPE).


Individuals with ME/CFS demonstrated smaller dO2Hb and dHHb than controls. However, after adjusting for TTI and change in total hemoglobin (delta (d)tHb), differences in dO2Hb and dHHb were reduced, with large overlapping variances. RPE was significantly higher for cases than controls, particularly at rest.


Relative to controls, participants with ME/CFS demonstrated higher RPE, lower TTI, and reduced dO2Hb and dHHb during repetitive handgrip exercise, although considerable variance was observed. With further study, submaximal exercise testing may prove useful for stratifying patients with a lower propensity for inducing PEM, and have the ability to establish baseline intensities for exercise prescription.

From Immunology and Immunogenetics Insights, 26 May 2015 (Full text available).

Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients

Sonya Marshall-Gradisnik(1,2), Peter Smith(2), Bernd Nilius(3) and Donald R. Staines(2)
1) School of Medical Science, Griffith University, Gold Coast, Australia.
2) The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Gold Coast, Australia.
3) Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, KU Leuven, Belgium.



Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disorder characterized by debilitating fatigue accompanied by pain and impairments in memory, cognition, and concentration.

Acetylcholine (ACh) has a plethora of roles in neuronal and neuromuscular transmission. There are two types of ACh receptors, muscarinic and nicotinic, comprising 17 different subunits of thenicotinic ACh receptor (nAChR) and five different subtypes of the muscarinic receptor (mAChR) that have been identified in humans.

The purpose of this study was to determine the role of ACh receptor (nAChRs and mAChRs) single nucleotide polymorphisms (SNPs) in CFS/ME patients.


One-hundred and fifteen CFS/ME patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years) participated in this study, where CFS/ME patients were defined according to the 1994 Center for Disease Prevention and Control (CDC) criteria. A total of 464 SNPs for nine mammalian ACh receptor genes (M1, M2, M3, M4, M5, alpha 2, 5, 7, and 10) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software.


Seventeen SNPs were significantly associated with CFS/ME patients compared with the controls. Nine of these SNPs were associated with mAChRM3 (rs4463655; P = 0.00281, rs589962; P = 0.00348, rs1072320; P = 0.00371, rs7543259; P = 0.00513, rs6661621; P = 0.00536 rs7520974; P = 0.0167, rs726169; P = 0.02349, rsrs6669810; P = 0.02361, rsrs6429157; P = 0.0375), while the remainder were
associated with nAChR alpha 10 (rs2672211; P = 0.0107, rs2672214; P = 0.0108, rs2741868; P = 0.01185, rs2741870; P = 0.01281, rs2741862; P = 0.03043), alpha 5 (rs951266; P = 0.01153; rs7180002, P = 0.03682), and alpha 2 (rs2565048; P = 0.01403).


The data from this pilot study suggest an association between ACh receptors, predominantly M3 and CFS. ACh receptor SNPs may contribute to the pathomechanism of CFS/ME.

From The Journal of Immunology, 1 May 2015.

Assessment of the Fc receptor CD16A of NK cells of CFS patients for potential to mediate ADCC activity (HUM1P.303)

Isabel Silvestre(1), Daniel Peterson(2), Douglas Redelman(3), Stephen Anderson(4) and Dorothy Hudig(1)
1) Microbiology and Immunology, Univ of Nevada School of Medicine, Reno, NV
2) Sierra Internal Medicine, Incline, NV
3) Physiology, University of Nevada School of Medicine, Reno, NV
4) NCI NIH, Frederick, MD


Natural killer (NK) cytotoxicity of chronic fatigue syndrome (CFS) patients is decreased, as reported by several laboratories. This observation led us to query whether the NK cells also lack antibody-dependent cell-mediated cytotoxicity (ADCC). NK cells have the IgG Fc-receptor CD16A that mediates ADCC.

To assess potential ADCC effectors, we examined the peripheral blood of 11 CFS patients from a Lake Tahoe cohort that met the Fukuda standards for CFS and had low SF36 scores. Healthy controls were age- and gender-matched.

We stained peripheral blood cells for CD16A with mAb clone 3G8 and for CD3, CD56, and perforin, then assessed the cells by flow cytometry.

We found that the percentages of NK cells expressing CD16A were slightly lower for CFS patients 86.0 +/- 11.5% vs. controls 93.0 +/- 6.6% (P=0.08). The median fluorescent indices (MFIs) of CD16A were lower,72% of the values for the CFS patients, 9342 +/- 3233 vs. control 12929 +/- 4425, though not statistically significant (P<0.17). Intracellular staining for perforin in the CD16Apos cells was similar for patients and controls.Our data indicate that a larger sampling of CFS patients vs. controls is required to determine if the fractions of CD16Apos NK cells and the levels of CD16A on these cells differs. These two observations are both in the direction of compromising ADCC activity of patients. In addition, a bias in F over V allelic variants of CD16A might add to impairment, since the F allele confers reduced ADCC.

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