Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic fatigue syndrome

Abstract

Background: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms. Purpose: To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response. Methods: The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes -- natural killer (NK) cells (CD3-CD16+ and CD3-CD56+) and naïve T cells (CD4+CD45RA+) -- to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue.. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes. Results: Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3-CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms. Conclusion: These findings suggest that lymphocytes are modestly related to clinical outcomes over time.

Exercise alters brain activation in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Emphasis has been placed on post-exertional malaise, the characteristic exacerbation of symptoms following minimal effort, as a distinguishing feature of ME/CFS ( Carruthers et al , 2003 ). Biomarker studies suggest roles for cytokines ( Hornig et al , 2016 ), reduced natural killer cell activity ( Caligiuri et al , 1987 ; Mehalick et al , 2018 ), microRNAs ( Baraniuk and Shivapurkar, 2017 ), metabolomics ( Armstrong et al , 2014 ), gut microbiome ( Du Preez et al , 2018 ), neuroinflammation with microglial activation ( Nakatomi et al , 2014 ) and brainstem connectivity and myelination changes ( Barnden et al , 2016 , 2018 , 2019 ).…”

Pilot assessment of low NK cell-mediated ADCC andFCGR3Agenetics in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Based on inclusion of family members without ME/CFS as controls, low ADCC is unsuitable as a diagnostic biomarker

“…The inclusion of family members without ME/CFS as controls in the present report resulted in the rapid identification of unsuitable diagnostic ADCC biomarkers et al observed in 1987 that CFS patients have low NK activity [28]. Studies followed that reported low NK function (reviewed [29], also [30][31][32][33]), NK phenotypes consistent with lower NK cell function (e.g., low perforin [34]; low granzyme B [33]; lower frequency of the more cytotoxic CD56dim NK cells [35], and low ERK1/2 kinase [36]), and fewer blood NK cells in patients during CFS disease episodes [37]. In contrast, a recent Scandinavian study with large numbers of ME/CFS patients indicates that many CFS patients have normal NK activity and that low NK activity is unsuitable as a biomarker for this disease [38].…”