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Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndr


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J Transl Med. 2013 Mar 20;11(1):68. [Epub ahead of print]
Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome.

Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, Garcia-Quintana AM, Castro-Marrero J, Negredo E, Clotet B, Cabrera C, Blanco J.


Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability.

Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups.

CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals.

Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.

I concluded decades ago something was wrong with Tcell function.

Levamisole improves Tcell function.


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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.

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 (CD56
bright and CD56dim) and regulatory T cells

expressing FoxP3 transcription factor.

Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-g, TNF-a,

+CD25+ T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NK phenotypes, in

particular the CD56
bright 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.

Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients

with potential for an application as a diagnostic tool.