Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis

Abstract

BackgroundChronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time. This study investigates Natural Killer (NK) cell cytotoxic activity, NK cell subsets (CD56brightCD16- and CD56dimCD16+) and cytokines, over the course of a12 month period in patients with CFS/ME.MethodsThe participants in the study comprised 65 (47.2 ± 11.5 years) CFS/ME participants and 21 (45.2 ±9.3 years) non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1), 6 (T2) and 12 months (T3). Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells.ResultsNK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16- NK cells at both T1 and T2. Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-γ and TNF-α at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non-fatigued controls. Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56brightCD16- NK cells were much lower at T2 compared to T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to T1 and T3.ConclusionThese results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study.

Immune Abnormalities in Patients Meeting New Diagnostic Criteria for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

“…NK cell activity is a promising candidate for CFS/ME diagnostic marker. A global impairment in NK activity has consistently been observed in CFS/ME patients [7,15,16,19,20]. This suggests an inability of the NK cells in CFS/ME patients to clear viral and other microbial infections and also a prevalence of recurring viral infections.…”

“…A particularly consistent finding in CFS/ME is found in the immunological system, as Natural Killer (NK) cell activity has been identified as an important marker that is significantly reduced across all patients [7]. Increases in regulatory T cells (Tregs) have also been reported, while cytokines remain controversial.…”

Putative Prophylaxes of Aloe Vera Juice with L-arginine to Chronic Fatigue Syndrome

“…In conclusion, these results confirm decreases in immune function in CFS/ME patients suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosis CFS/ME as it was consistently decreased during the course of the 12 months study [18] . Campbell KS.…”

Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

“…This disabling illness is associated with poor memory and concentration; metabolic, cardiac, gastrointestinal, and immune dysfunction; and muscle fatigue often described as neuroimmune exhaustion and post-exertional malaise. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] We have previously identified single-nucleotide polymorphisms (SNPs) in genes for transient receptor potential (TRP) ion channels and acetylcholine receptors (AChRs), which have important roles in calcium (Ca 2+ ) and acetylcholine (ACh) signaling. [19][20][21] From this same cohort of patients, we now report additional data showing the prevalence of both TRP melastatin M3 (TRPM3) ion channel and muscarinic ACh M3 receptor (mAChM3R) SNP genotypes in patients with CFS/ME ( Table 1).…”