Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, 2011, Brenu et al

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Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Ekua W Brenu, Mieke L van Driel, Don R Staines, Kevin J Ashton, Sandra B Ramos, James Keane, Nancy G Klimas & Sonya M Marshall-Gradisnik

Published: 28 May 2011

Background
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers) in CFS/ME patients.

Methods
We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK) and CD8+T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4+T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2), levels of NK phenotypes (CD56bright and CD56dim) and regulatory T cells expressing FoxP3 transcription factor.

Results
Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NK phenotypes, in particular the CD56bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients.

Conclusions
Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

Link | PDF (Journal of Translational Medicine) [Open Access]

 

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Old study, but posting because of more recent research into T cell exhaustion. It's hard to know if changes in the observed phenotypes of the T cells actually affect their ability to kill cells, but this study found that CD8 cells from people with ME/CFS (CDC criteria) showed decreased killing activity:

NK and CD8+T (n = 71) cytotoxic activity measured as the ability of NK and CD8+T cells to effectively lyse K562 and P815 cells respectively was significantly decreased (p < 0.05) among the CFS/ME patients compared to the control subjects (Figure 2).

Similarly granzyme A expression was significantly decreased in both the NK and CD8+T cells in the CFS/ME population. However, IFN-γ and granzyme K were decreased only in the NK cells of the CFS/ME group compared to the healthy controls as shown in Figure 3A and 3B.

I'm trying to find other studies that tested this in CD8 cells, but haven't found any yet. There's the below study that had a null result, but as far as I can tell, they didn't test killing activity directly, just measured the killing chemicals (granzyme, perforin). And the following study was also excluded from an NK cell cytotoxicity meta-analysis because "they used (a) frozen cells even though frozen NK cells do not preserve cytotoxicity after being thawed", so that might be the reason for the null result in T cells as well.

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients (2017, Frontiers in Immunology)

So it's only one study that seems to have tested this, but I think it's plausible that if decreased NK cell cytotoxicity turns out to be a real finding, that there's a common cause making T cells less cytotoxic as well.