Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis
Ekua W Brenu, Mieke L van Driel, Donald R Staines, Kevin J Ashton, Sharni L Hardcastle, James Keane, Lotti Tajouri, Daniel Peterson, Sandra B Ramos and Sonya M Marshall-Gradisnik
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Journal of Translational Medicine 2012, 10:88 doi:10.1186/1479-5876-10-88
Published: 9 May 2012
Abstract (provisional)
Background
Chronic 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.
Methods
The 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.
Results
NK 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-gamma and TNF-alpha 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 the T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to the T1 and T3.
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 diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Ekua W Brenu, Mieke L van Driel, Donald R Staines, Kevin J Ashton, Sharni L Hardcastle, James Keane, Lotti Tajouri, Daniel Peterson, Sandra B Ramos and Sonya M Marshall-Gradisnik
For all author emails, please log on.
Journal of Translational Medicine 2012, 10:88 doi:10.1186/1479-5876-10-88
Published: 9 May 2012
Abstract (provisional)
Background
Chronic 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.
Methods
The 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.
Results
NK 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-gamma and TNF-alpha 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 the T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to the T1 and T3.
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 diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
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