Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients

Abstract

BackgroundMyalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no established biological markerof the syndrome. The etiology is unknown and its pathogenesis appears to be multifactorial. Various stressors, including intense physical activity, severe infection, and emotional stress are reported in the medical history of ME/CFS patients which raises the question whether any physiological and biological abnormalities usually found in these patients could be indicative of the etiology and/or the quality-of-life impairment.MethodsThirty-six patients and 11 age-matched healthy controls were recruited. The following variables that appear to address common symptoms of ME/CFS were studied here: (1) muscle fatigue during exercise has been investigated by monitoring the compound muscle action potential (M-wave); (2) the excessive oxidative stress response to exercise was measured via two plasma markers (thiobarbituric acid reactive substances: TBARS; reduced ascorbic-acid: RAA); (3) a potential inflammatory component was addressed via expression of CD26 on peripheral blood mononuclear cells; (4) quality-of-life impairment was assessed using the London Handicap Scale (LHS) and the Medical Outcome Study Short Form-36 (SF-36). The medical history of each patient, including the presence of stressors such as intense sports practice, severe acute infection and/or severe emotional stress was documented.ResultsWe observed that: (1) there were striking differences between cases and controls with regard to three biological variables: post-exercise M-wave, TBARS variations and CD26-expression at rest; (2) each of these three variables correlated with the other two; (3) abnormalities in the biomarkers associated with health-related quality of life: the LHS score was negatively correlated with the exercise-induced TBARS increase and positively correlated with CD26-expression while the pain component of SF-36 was negatively correlated with CD26-expression; (4) the TBARS increase and the M-wave decrease were the highest, and the CD26-expression level the lowest in patients who had been submitted to infectious stressors.ConclusionIn ME/CFS patients, severe alterations of the muscle excitability, the redox status, as well as the CD26-expression level are correlated with a marked impairment of the quality-of-life. They are particularly significant when infectious stressors are reported in the medical history.

Inflammation correlates with symptoms in chronic fatigue syndrome

“…Many studies have found evidence of oxidative stress in CFS patients: increased levels of isoprostanes, peroxides and superoxide (that correlate with the severity of symptoms), reduced levels of antioxidants (including α-tochopherol), and impaired redox status as reflected in plasma levels of thiobarbituric acid reactive substances (which are correlated with the severity of symptoms) (10). Increased nitrosative stress has also been documented by increased levels of inducible nitric oxide synthase, nitric oxide, peroxynitrite, and nitrate.…”

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

“…Bipolar Ag-AgCl surface electrodes (Medtronic, 13 L 20 Skovlunde, Denmark) were used to measure EMG voltage from the RF and FDL muscles on the dominant side of the body, as in previous studies [8][9][10][11][12][13]. The EMG signal was amplified (Nihon Kohden, Tokyo, Japan; common mode rejection ratio, 90 dB; input impedance, 100 mOhm; gain, 1000-5000) with a frequency band ranging from 10-10,000 Hz.…”

“…All patients underwent an exercise session on a cycle ergometer up to their maximal work rate supported for a 1-min period, often limited by muscle fatigue. As in our previous studies [8][9][10][11]13], the protocol consisted of: (i) a 2-min rest period, during which all variables were measured and venous blood samples collected; (ii) a 1-min 20-W work load period used to reach the 1 Hz cycling frequency; (iii) a work period; and (iv) a 10-min recovery period. During the work period, the load was increased by 20 W every 60 s until fatigue obliged the subject to stop the exercise.…”

“…Potential causes of muscle dysfunction in ME/CFS patients may include oxidative stress with reduced heat-shock protein production. Experimental evidence indicates that exercising skeletal muscles are often affected in ME/CFS Page 2 of 8 Jammes et al J Transl Med (2020) 18:173 because marked alterations in myopotential occur in response to direct muscle stimulation (M-wave) [5][6][7][8][9][10][11]. M-wave alterations show impaired muscle membrane excitability and begin early in the exercising muscles before culminating during the 10-min recovery period [6][7][8].…”

“…Fulle et al [7] observed a dysregulation of the Na + /K + ATPase pump in ME/CFS patients and suggested that this dysregulation could result from increased fluidity of the sarcoplasmic reticulum membrane in relation to the excessive production of reactive oxygen species (ROS). Indeed, an increase in both resting levels and exerciseinduced production of ROS is often found in ME/CFS patients [8][9][10][11][14][15][16]. In these studies, thiobarbituric acid reactive substance (TBARS), an element related to overall redox equilibrium and a marker of lipid peroxidation, was used on several occasions to measure oxidative stress.…”