Tuesday, August 26, 2014

Reduced NK cell cytotoxic activity in patients with CFS/ME



Characterization of Natural Killer cell phenotypes
in chronic fatigue syndrome/myalgic encephalomyelitis.
J Clin Cell Immunol. 2014. 5: 223. doi:10.4172/2155-9899.1000223
Huth TK, Brenu EW, Nguyen T, Hardcastle SL, Johnston S, Ramos S, Staines DR, Marshall-Gradisnik SM.


Received date: April 22, 2014,
Accepted date: June 7, 2014,
Published date: June 14, 2014


Abstract

Objective:

Natural Killer (NK) cells are classified into different phenotypes
according to the expression of the surface markers CD56 and CD16.

Each NK cell phenotype has a role in the immune response
through cytotoxic activity or cytokine production.

Reduced NK cell cytotoxic activity is a consistent finding
in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) and
investigations into the potential causes of reduced NKcell cytotoxic activity
have predominantly focused on total NK cells.

The purpose of this study was
to investigate and characterize four NK cell phenotypes in CFS/ME.


Methods:

Twenty nine CFS/ME patients (mean age ± SEM=48.28 ± 2.63)
meeting the 1994 Fukuda definition
and 27 healthy controls (mean age ± SEM=49.15 ± 2.51)
were included in this study.

Flow cytometric protocols identified
CD56brightCD16-/dim, CD56dimCD16-, CD56dimCD16+ or CD56-CD16+ NK cells
for the measurement of surface markers
including adhesion moleculesCD2, CD18, CD11a, CD11b and CD11c,
natural cytotoxicity receptors, Killer Immunoglobulin Like Receptors,
signalling lymphocytic activation molecules and cell maturation (CD57).

Following stimulation,
NK cell phenotype expression of CD107a and CD107b
was measured as a marker for degranulation.

Intracellular staining measured lytic proteins
including perforin, Granzyme A and Granzyme B
in the four NK cell phenotypes.

Results:


from CFS/ME patients.

from CFS/ME patients was significantly increased.


Conclusion:

This is the first study to characterize
four NK cell phenotypes in CFS/ME
by investigating surface and intracellular molecules
necessary for NK cell effector function.

The data suggests that
a combination of impairments in CD56dimCD16+ NK cells from CFS/ME patients
may contribute to reduced cytotoxic activity of this phenotype.


Keywords:

Natural Killer cell; Phenotypes; Chronic Fatigue Syndrome; Cytotoxic activity;
Adhesion molecules; Degranulation; Granzyme B; Cell maturation





Tuesday, August 12, 2014

Chemical changes in immune cell DNA from ME/CFS patients

@ plosone:
RESEARCH ARTICLE

DNA Methylation Modifications Associated with Chronic Fatigue Syndrome

  • Wilfred C. de Vega,
  •  
  • Suzanne D. Vernon,
  •  
  • Patrick O. McGowan mail

  • Published: August 11, 2014
  • DOI: 10.1371/journal.pone.0104757

Abstract

Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Gene ontology (GO) and network analysis of differentially methylated genes was performed to determine potential biological pathways showing changes in DNA methylation in CFS. We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology.

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