Gene expression alterations at baseline and following exercise in patients with ME/CFS, correlating with fatigue and pain

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome.

Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC.

Department of Anesthesiology, University of Utah, Salt Lake City, UT The Brain Institute, University of Utah, Salt Lake City, UT Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT Department of Exercise and Sprt Science, University of Utah, Salt Lake City, UT.

Abstract
Light AR, Bateman L, Jo D, Hughen RW, VanHaitsma TA, White AT, Light KC (University of Utah Dept. Anesthesiology, Dept. Neurobiology and Anatomy, Dept. Exercise and Sport Science) Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome. Objectives: To determine mRNA expression differences in genes involved in signaling and modulating sensory fatigue, and muscle pain in patients with Chronic Fatigue Syndrome (CFS) and Fibromyalgia Syndrome (FM) at baseline, and following moderate exercise. Design: Forty eight Patients with CFS-only, or CFS with comorbid FM, 18 Patients with FM that did not meet criteria for CFS, and 49 healthy Controls underwent moderate exercise (25 minutes at 70% maximum age predicted heart-rate). Visual-analogue measures of fatigue and pain were taken before, during, and after exercise. Blood samples were taken before, and 0.5, 8, 24, and 48 hours after exercise. Leukocytes were immediately isolated from blood, number coded for blind processing and analyses, and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic, and immune functions was compared between groups at baseline, and following exercise. Changes in amounts of mRNA were correlated with behavioral measures, and functional clinical assessments. Results: No gene expression changes occurred following exercise in Controls. In 71% of CFS patients, moderate exercise increased most sensory and adrenergic receptor's and one cytokine gene's transcription for 48 hours. These post-exercise increases correlated with behavioral measures of fatigue and pain. In contrast, for the other 29% of CFS patients, adrenergic α-2A receptor's transcription was decreased at all time points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM only patients showed no post-exercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than Controls. Conclusions: At least two subgroups of CFS patients can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the CFS patients with orthostatic intolerance, showed no post-exercise increases in any gene, and was defined by decreases in mRNA for α-2A. FM only patients can be identified by baseline increases in 3 genes. Post-exercise increases for 4 genes meet published criteria as an objective biomarker for CFS, and could be useful in guiding treatment selection for different subgroups.