by Sasha Nimmo
Queensland scientists looked at blood samples from patients with moderate and severe Myalgic Encephalomyelitis (International Consensus Criteria). In the severe ME patients, they found 37 genes were significantly upregulated and 55 genes were significantly downregulated compared with nonfatigued controls. However, there was no difference in expression of protein kinase genes between moderate ME patients and controls.
“This current paper reports novel results of far reaching importance for CFS/ME diagnosis and possible pathology. The paper describes world first discoveries of kinase gene dysregulation associated with changes in calcium ion function. This research leads from previous significant papers we have recently published involving research into calcium ion channels in CFS/ME,” the scientists said on their Facebook page.
The paper by Chack, Staines, Johnston and Marshall-Gradisnik, Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients, was published in Gene Regulation and Systems Biology, July 2016. (The authors refer to CFS/ME in the paper but the criteria they use, ICC, “recommends that only the name ‘myalgic encephalomyelitis’ be used to identify patients meeting the ICC because a distinctive disease entity should have one name. Those who fulfill the criteria have ME; those who do not would remain in the more encompassing CFS classification.”)
Natural killer (NK) cell dysfunction, in particular reduced NK cytotoxic activity, is a consistent finding in patients with ME, say the scientists from the National Centre for Neuroimmunology and Emerging Diseases and Menzies Health Institute at Griffith University, Australia.
In this study, there were 92 protein kinase genes differentially regulated in the NK cells of ME patients, compared with healthy nonfatigued controls. These genes are involved in cell signaling and metabolic pathways including inflammation.
What are protein kinases?
Protein kinases are key regulators of cell function that constitute one of the largest and most functionally diverse gene families. By adding phosphate groups to substrate proteins, they direct the activity, localization and overall function of many proteins, and serve to orchestrate the activity of almost all cellular processes. Kinases are particularly prominent in signal transduction and co-ordination of complex functions such as the cell cycle. (from Cell Signal)
In severe ME patients, dysfunction in protein kinase genes may contribute to impairments in NK cell intracellular signaling and effector function.
The study says while this shows functional impairment in NK cytotoxic activity and immunological dysfunction, kinases are located throughout cells in the body and may be associated with other clinical manifestations reported in ME.
“The kinase genes identified in this study control a large number of process networks within cells affecting synaptic function, signal transduction, inflammation pathways, apoptosis, muscle contraction, microtubule cytoskeleton spindle assembly, circadian rhythm, calcium transport, and nitric oxide signaling. Metabolic effects, predominantly insulin gene expression pathways, were identified. Protein phosphorylation and protein modification pathways predominated in gene association analysis.
“Kinase perturbations suggest the likely demonstration of an inflammatory profile and other dysregulated physiological mechanisms, adding to widespread inflammatory mechanism dysregulation in virtually all cells.”
Severe ME definition
Severity of ME was defined according to Dr Bell’s disability scale that ranges from 100% (no symptoms) to 0% (severe symptoms). Patients categorised as moderate ME scored more than 30%. Severe ME patients scored less than 30% and were considered housebound or bedridden. Patients’ disability was also self-reported using the fatigue severity scale (Measuring Health and Disability: Manual for WHO Disability Assessment Schedule, World Health Organization 2010) and the MOS 36-item short-form health survey (SF-36) Med Care 1992.
The study says impaired neurological and motor control are common symptoms associated with ME and suggest calcium (Ca2+) and kinase signaling dysregulation be further investigated in the central nervous system, given the high dependence on Ca2+ signaling for glial and neuronal cell functioning and their potential role in the pathomechanism of ME.
To read other Griffith University studies, here is a list of publications.