Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients.
BACKGROUND
The etiology and pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are unknown. However, natural killer (NK) cell dysfunction, in particular reduced NK cytotoxic activity, is a consistent finding in CFS/ME patients. Previous research has reported significant changes in intracellular mitogen-activated protein kinase pathways from isolated NK cells. The purpose of this present investigation was to examine whether protein kinase genes have a role in abnormal NK cell intracellular signaling in CFS/ME.


METHODS
Messenger RNA (mRNA) expression of 528 protein kinase genes in isolated NK cells was analyzed (nCounter GX Human Kinase Kit v2 (XT); NanoString Technologies) from moderate (n = 11; age, 54.9 ± 10.3 years) and severe (n = 12; age, 47.5 ± 8.0 years) CFS/ME patients (classified by the 2011 International Consensus Criteria) and nonfatigued controls (n = 11; age, 50.0 ± 12.3 years).


RESULTS
The expression of 92 protein kinase genes was significantly different in the severe CFS/ME group compared with nonfatigued controls. Among these, 37 genes were significantly upregulated and 55 genes were significantly downregulated in severe CFS/ME patients compared with nonfatigued controls.


CONCLUSIONS
In severe CFS/ME patients, dysfunction in protein kinase genes may contribute to impairments in NK cell intracellular signaling and effector function. Similar changes in protein kinase genes may be present in other cells, potentially contributing to the pathomechanism of this illness.
School of Medical Science, Griffith University, QLD, Australia.; The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Australia.
Anu
A
Chacko
The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Australia.
Donald R
DR
Staines
School of Medical Science, Griffith University, QLD, Australia.; The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Australia.
Samantha C
SC
Johnston
School of Medical Science, Griffith University, QLD, Australia.; The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, QLD, Australia.
Sonya M
SM
Marshall-Gradisnik
NK cells; calcium-dependent kinase genes; chronic fatigue syndrome; gene expression; protein kinase genes