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Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Ekua W Brenu1, Kevin J Ashton, Mieke van Driel
1Faculty of Health Science and Medicine, Population Health and Neuroimmunology Unit, Bond University, Robina, Queensland, Australia. ekbrenu@bond.edu.au
Background:
Immune dysfunction associated with a disease often has a molecular basis. A novel group of molecules known as microRNAs (miRNAs) have been associated with suppression of translational processes involved in cellular development and proliferation, protein secretion, apoptosis, immune function and inflammatory processes. MicroRNAs may be implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), where immune function is impaired. The objective of this study was to determine the association between miRNAs in cytotoxic cells and CFS/ME.
Methods:
Natural Killer (NK) and CD8(+)T cells were preferentially isolated from peripheral blood mononuclear cells from all participants (CFS/ME, n=28; mean age=41.8±9.6 years and controls, n=28; mean age=45.3±11.7 years), via negative cell enrichment. Following total RNA extraction and subsequent synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of nineteen miRNAs.
Results:
There was a significant reduction in the expression levels of miR-21, in both the NK and CD8(+)T cells in the CFS/ME sufferers. Additionally, the expression of miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223 and miR-191 was significantly decreased in NK cells of CFS/ME patients in comparison to the non-fatigued controls.
Limitations:
The results from these investigations are not yet transferable into the clinical setting, further validatory studies are now required.
Conclusions:
Collectively these miRNAs have been associated with apoptosis, cell cycle, development and immune function. Changes in miRNAs in cytotoxic cells may reduce the functional capacity of these cells and disrupt effective cytotoxic activity along with other immune functions in CFS/ME patients.
Insights
MicroRNAs (miRNAs) are implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This study found reduced expression of specific miRNAs in cytotoxic cells of CFS/ME patients, suggesting a role in immune dysfunction.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Immune dysfunction in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) may stem from molecular factors.
- MicroRNAs (miRNAs) regulate gene expression and are involved in immune processes, cellular development, and apoptosis.
- Impaired immune function in CFS/ME suggests a potential role for miRNAs.
Purpose of the Study:
- To investigate the association between microRNAs (miRNAs) in cytotoxic cells and CFS/ME.
- To determine if specific miRNA expression levels differ between individuals with CFS/ME and healthy controls.
Main Methods:
- Peripheral blood mononuclear cells were isolated from CFS/ME patients (n=28) and controls (n=28).
- Natural Killer (NK) and CD8(+)T cells were enriched using negative cell selection.
- Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was employed to quantify the expression of nineteen miRNAs.
Main Results:
- A significant downregulation of miR-21 was observed in both NK and CD8(+)T cells of CFS/ME patients.
- Expression of miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223, and miR-191 was significantly decreased in NK cells of CFS/ME patients compared to controls.
- These findings indicate altered miRNA profiles in cytotoxic cells associated with CFS/ME.
Conclusions:
- The identified miRNAs are linked to apoptosis, cell cycle, development, and immune function.
- Reduced miRNA expression in cytotoxic cells may impair their functional capacity and disrupt immune responses in CFS/ME.
- Further validation studies are necessary before clinical application.
