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

Ekua W Brenu, Kevin J Ashton, Mieke van Driel, Donald R Staines, Daniel Peterson, Gunn M Atkinson, Sonya M Marshall-Gradisnik

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Abstract

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.

Original languageEnglish
Pages (from-to)261-9
Number of pages9
JournalJournal of Affective Disorders
Volume141
Issue number2-3
DOIs
Publication statusPublished - 10 Dec 2012

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Chronic Fatigue Syndrome
MicroRNAs
Biomarkers
Lymphocytes
Natural Killer T-Cells
Apoptosis
Reverse Transcriptase Polymerase Chain Reaction
Natural Killer Cells
Blood Cells
Cell Cycle
Complementary DNA

Cite this

Brenu, E. W., Ashton, K. J., van Driel, M., Staines, D. R., Peterson, D., Atkinson, G. M., & Marshall-Gradisnik, S. M. (2012). Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Journal of Affective Disorders, 141(2-3), 261-9. https://doi.org/10.1016/j.jad.2012.03.037
Brenu, Ekua W ; Ashton, Kevin J ; van Driel, Mieke ; Staines, Donald R ; Peterson, Daniel ; Atkinson, Gunn M ; Marshall-Gradisnik, Sonya M. / Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. In: Journal of Affective Disorders. 2012 ; Vol. 141, No. 2-3. pp. 261-9.
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abstract = "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.",
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Brenu, EW, Ashton, KJ, van Driel, M, Staines, DR, Peterson, D, Atkinson, GM & Marshall-Gradisnik, SM 2012, 'Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis' Journal of Affective Disorders, vol. 141, no. 2-3, pp. 261-9. https://doi.org/10.1016/j.jad.2012.03.037

Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. / Brenu, Ekua W; Ashton, Kevin J; van Driel, Mieke; Staines, Donald R; Peterson, Daniel; Atkinson, Gunn M; Marshall-Gradisnik, Sonya M.

In: Journal of Affective Disorders, Vol. 141, No. 2-3, 10.12.2012, p. 261-9.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cytotoxic lymphocyte microRNAs as prospective biomarkers for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

AU - Brenu, Ekua W

AU - Ashton, Kevin J

AU - van Driel, Mieke

AU - Staines, Donald R

AU - Peterson, Daniel

AU - Atkinson, Gunn M

AU - Marshall-Gradisnik, Sonya M

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2012/12/10

Y1 - 2012/12/10

N2 - 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.

AB - 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.

U2 - 10.1016/j.jad.2012.03.037

DO - 10.1016/j.jad.2012.03.037

M3 - Article

VL - 141

SP - 261

EP - 269

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

SN - 0165-0327

IS - 2-3

ER -