Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Faculty of Health Science and Medicine, Bond University, Robina, Queensland, Australia. Electronic address: .
Journal of Affective Disorders (Impact Factor: 3.38). 05/2012; 141(2-3):261-9. DOI: 10.1016/j.jad.2012.03.037
Source: PubMed


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.
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±9.6years and controls, n=28; mean age=45.3±11.7years), 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.
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.
The results from these investigations are not yet transferable into the clinical setting, further validatory studies are now required.
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.

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    • "In addition to fatigue, CFS/ME is associated with a wide range of symptoms, including post-exertional malaise, pain, unrefreshing sleep, and cognitive impairment [11]. Alterations in both the innate and acquired immune systems have been reported [12] [13] [14] [15] [16] [17]. Disease clustering and even small epidemics have been described [18] [19] [20] [21] [22] [23] [24]. "
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    ABSTRACT: Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination. Methods: Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression. Results: The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91-1.04), while it was 2.04 (95% CI: 1.78-2.33) after being diagnosed with influenza infection during the peak pandemic period. Conclusions: Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.
    Vaccine 10/2015; DOI:10.1016/j.vaccine.2015.10.018 · 3.62 Impact Factor
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    • "In cancer-associated fibroblasts, Aprelikova et al. showed that miR-148a was downregulated compared with matched normal tissue fibroblasts established from patients with endometrial cancer and wingless-type MMTV integration site family, member 10B (WNT10B) was a direct target of miR-148a [42]. In some nontumor diseases, such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), miR-152 was significantly decreased in NK cells of CFS/ME patients compared with nonfatigued controls [25]. "
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    ABSTRACT: MicroRNAs(miRNA) are noncoding RNAs of about 19--23 nucleotides that are crucial for many biological processes. Members of the microRNA-148/152(miR-148/152) family, which include microRNA-148a(miR-148a), microRNA-148b(miR-148b), and microRNA-152(miR-152), are expressed differently in tumor and nontumor tissues and are involved in the genesis and development of disease. Furthermore, members of the miR-148/152 family are important in the growth and development of normal tissues. Members of the miR-148/152 family regulate target genes and are regulated by methylation of CPG islands. In this review, we report recent studies on the expression of members of the miR-148/152 family, methylation of CPG islands, and their target genes in different diseases, as well as in normal tissues.
    Molecular Cancer 05/2013; 12(1):43. DOI:10.1186/1476-4598-12-43 · 4.26 Impact Factor
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    • "Data for the role for NK cell-intrinsic miRNA in these diseases is limited, but an important area of active investigation. For example , it was recently found that in patients with chronic fatigue syndrome, certain highly expressed NK miRNAs, such as miR- 21, were significantly decreased in NK cells (Brenu et al., 2012). Most of the existing literature regarding the role of NK miRNAs in disease focuses on NK cell malignancies. "
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    ABSTRACT: Natural killer (NK) cells are innate immune lymphocytes critical for host defense against viral infection and surveillance against malignant transformation. MicroRNAs (miRNAs) are a family of small, non-coding RNAs that regulate a wide variety of cellular processes. Recent advances have highlighted the importance of miRNA-mediated post-transcriptional regulation in NK cell development, maturation, and function. This review focuses on several facets of this regulatory mechanism in NK cells: (1) the expressed NK cell miRNA transcriptome; (2) the impact of total miRNA deficiency on NK cells; (3) the role of specific miRNAs regulating NK cell development, survival, and maturation; (4) the intrinsic role of miRNAs regulating NK cell function, including cytokine production, proliferation, and cytotoxicity; and (5) the role of NK cell miRNAs in disease. Currently our knowledge of how miRNAs regulate NK cell biology is limited, and thus we also explore key open questions in the field, as well as approaches and techniques to ascertain the role of individual miRNAs as important molecular regulators.
    Frontiers in Immunology 02/2013; 4:44. DOI:10.3389/fimmu.2013.00044
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