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Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients

Authors: Sharni Lee Hardcastle, Ekua Weba Brenu, Samantha Johnston, Thao Nguyen, Teilah Huth, Sandra Ramos, Donald Staines, Sonya Marshall-Gradisnik

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

Background

Research has identified immunological abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), a heterogeneous illness with an unknown cause and absence of diagnostic test. There have been no CFS/ME studies examining innate and adaptive immune cells longitudinally in patients with varying severities. This is the first study to investigate immune cells over 6 months while also examining CFS/ME patients of varying symptom severity.

Methods

Participants were grouped into 18 healthy controls, 12 moderate and 12 severe CFS/ME patients and flow cytometry was used to examine cell parameters at 0 and 6 months.

Results

Over time, iNKT CD62L expression significantly increased in moderate CFS/ME patients and CD56bright NK receptors differed in severe CFS/ME. Naïve CD8+T cells, CD8CD4 and CD56CD16 iNKT phenotypes, γδ2T cells and effector memory subsets were significantly increased in severe CFS/ME patients at 6 months. Severe CFS/ME patients were significantly reduced in CD56brightCD16dim NKG2D, CD56dimCD16 KIR2DL2/DL3, CD94CD11a γδ1T cells and CD62L+CD11a γδ1T cells at 6 months.

Conclusions

Severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8+T cell markers, NK cell receptors and γδT cells at 6 months. This highlights the importance of further assessing these potential immune biomarkers longitudinally in both moderate and severe CFS/ME patients.
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Literature
1.
go back to reference Rathmell JC, Thompson CB. Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell. 2002;109(2):S97–107.CrossRefPubMed Rathmell JC, Thompson CB. Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell. 2002;109(2):S97–107.CrossRefPubMed
2.
go back to reference Brenu EW, van Driel ML, Staines DR, Ashton KJ, Hardcastle SL, Keane J, et al. Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2012;10:88.PubMedCentralCrossRefPubMed Brenu EW, van Driel ML, Staines DR, Ashton KJ, Hardcastle SL, Keane J, et al. Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2012;10:88.PubMedCentralCrossRefPubMed
3.
go back to reference Barker E, Fujimura SF, Fadem MB, Landay AL, Levy JA. Immunologic abnormalities associated with chronic fatigue syndrome. Clin Infect Dis. 1994;18(Supplement 1):S136–41.CrossRefPubMed Barker E, Fujimura SF, Fadem MB, Landay AL, Levy JA. Immunologic abnormalities associated with chronic fatigue syndrome. Clin Infect Dis. 1994;18(Supplement 1):S136–41.CrossRefPubMed
4.
go back to reference Brenu E, Hardcastle S, Atkinson G, van Driel M, Kreijkamp-Kaspers S, Ashton K et al. Natural killer cells in patients with severe chronic fatigue syndrome. Autoimmun Highlights. 2013;4(3):1–12.CrossRef Brenu E, Hardcastle S, Atkinson G, van Driel M, Kreijkamp-Kaspers S, Ashton K et al. Natural killer cells in patients with severe chronic fatigue syndrome. Autoimmun Highlights. 2013;4(3):1–12.CrossRef
5.
go back to reference Brenu E, Johnston S, Hardcastle S, Huth T, Fuller K, Ramos S, et al. Immune abnormalities in patients meeting new diagnostic criteria for chronic fatigue syndrome/Myalgic Encephalomyelitis. J Mol Biomark Diagn. 2013;4(152.10):4172. Brenu E, Johnston S, Hardcastle S, Huth T, Fuller K, Ramos S, et al. Immune abnormalities in patients meeting new diagnostic criteria for chronic fatigue syndrome/Myalgic Encephalomyelitis. J Mol Biomark Diagn. 2013;4(152.10):4172.
6.
go back to reference Brenu EW, van Driel ML, Staines DR, Ashton KJ, Ramos SB, Keane J, et al. Immunological abnormalities as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2011;9:81.PubMedCentralCrossRefPubMed Brenu EW, van Driel ML, Staines DR, Ashton KJ, Ramos SB, Keane J, et al. Immunological abnormalities as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2011;9:81.PubMedCentralCrossRefPubMed
7.
go back to reference Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, et al. Screening NK-, B-and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. 2013;11:68.PubMedCentralCrossRefPubMed Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, et al. Screening NK-, B-and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. 2013;11:68.PubMedCentralCrossRefPubMed
8.
go back to reference Klimas NG, Salvato FR, Morgan R, Fletcher MA. Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol. 1990;28(6):1403–10.PubMedCentralPubMed Klimas NG, Salvato FR, Morgan R, Fletcher MA. Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol. 1990;28(6):1403–10.PubMedCentralPubMed
9.
10.
go back to reference Hardcastle S, Brenu E, Johnston S, Nguyen T, Huth T, Kaur M. Analysis of the relationship between immune dysfunction and symptom severity in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). J Clin Cell Immunol. 2014;5(190):2. Hardcastle S, Brenu E, Johnston S, Nguyen T, Huth T, Kaur M. Analysis of the relationship between immune dysfunction and symptom severity in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). J Clin Cell Immunol. 2014;5(190):2.
11.
go back to reference ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM, Schedlowski M, Heijnen CJ. Longitudinal analysis of pro-and anti-inflammatory cytokine production in severely fatigued adolescents. Brain Behav Immun. 2007;21(8):1063–74.CrossRefPubMed ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM, Schedlowski M, Heijnen CJ. Longitudinal analysis of pro-and anti-inflammatory cytokine production in severely fatigued adolescents. Brain Behav Immun. 2007;21(8):1063–74.CrossRefPubMed
12.
go back to reference Hardcastle SL, Brenu EW, Johnston S, Staines D, Marshall-Gradisnik S. Severity scales for use in primary health care to assess Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Health Care Women Int. 2014;1–16 [Epub ahead of print]. Hardcastle SL, Brenu EW, Johnston S, Staines D, Marshall-Gradisnik S. Severity scales for use in primary health care to assess Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Health Care Women Int. 2014;1–16 [Epub ahead of print].
13.
go back to reference Montoya CJ, Pollard D, Martinson J, Kumari K, Wasserfall C, Mulder CB, et al. Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11. Immunology. 2007;122(1):1–14.PubMedCentralCrossRefPubMed Montoya CJ, Pollard D, Martinson J, Kumari K, Wasserfall C, Mulder CB, et al. Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11. Immunology. 2007;122(1):1–14.PubMedCentralCrossRefPubMed
14.
go back to reference Aguinis H, Gottfredson RK, Joo H. Best-practice recommendations for defining, identifying, and handling outliers. Organ Res Methods. 2013;16(2):270–301.CrossRef Aguinis H, Gottfredson RK, Joo H. Best-practice recommendations for defining, identifying, and handling outliers. Organ Res Methods. 2013;16(2):270–301.CrossRef
15.
go back to reference Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–40.CrossRefPubMed Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–40.CrossRefPubMed
16.
go back to reference Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56 bright subset. Blood. 2001;97(10):3146–51.CrossRefPubMed Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56 bright subset. Blood. 2001;97(10):3146–51.CrossRefPubMed
17.
18.
go back to reference Huth T, Brenu E, Nguyen T, Hardcastle S, Johnston S. Characterization of natural killer cell phenotypes in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Clin Cell Immunol. 2014;5(223):2. Huth T, Brenu E, Nguyen T, Hardcastle S, Johnston S. Characterization of natural killer cell phenotypes in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Clin Cell Immunol. 2014;5(223):2.
19.
go back to reference Epling-Burnette PK, Bai F, Painter JS, Rollison DE, Salih HR, Krusch M, et al. Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors. Blood. 2007;109(11):4816–24.PubMedCentralCrossRefPubMed Epling-Burnette PK, Bai F, Painter JS, Rollison DE, Salih HR, Krusch M, et al. Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors. Blood. 2007;109(11):4816–24.PubMedCentralCrossRefPubMed
20.
go back to reference Roederer M, Dubs JG, Anderson MT, Raju PA, Herzenberg LA, Herzenberg LA. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Investig. 1995;95(5):2061.PubMedCentralCrossRefPubMed Roederer M, Dubs JG, Anderson MT, Raju PA, Herzenberg LA, Herzenberg LA. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Investig. 1995;95(5):2061.PubMedCentralCrossRefPubMed
21.
go back to reference Landay A, Lennette E, Jessop C, Levy J. Chronic fatigue syndrome: clinical condition associated with immune activation. Lancet. 1991;338(8769):707–12.CrossRefPubMed Landay A, Lennette E, Jessop C, Levy J. Chronic fatigue syndrome: clinical condition associated with immune activation. Lancet. 1991;338(8769):707–12.CrossRefPubMed
22.
go back to reference Caligiuri M, Murray C, Buchwald D, Levine H, Cheney P, Peterson D, et al. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immunol. 1987;139(10):3306–13.PubMed Caligiuri M, Murray C, Buchwald D, Levine H, Cheney P, Peterson D, et al. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J Immunol. 1987;139(10):3306–13.PubMed
23.
go back to reference Anane LH, Edwards KM, Burns VE, Zanten JJ, Drayson MT, Bosch JA. Phenotypic characterization of γδ T cells mobilized in response to acute psychological stress. Brain Behav Immun. 2010;24(4):608–14.CrossRefPubMed Anane LH, Edwards KM, Burns VE, Zanten JJ, Drayson MT, Bosch JA. Phenotypic characterization of γδ T cells mobilized in response to acute psychological stress. Brain Behav Immun. 2010;24(4):608–14.CrossRefPubMed
24.
25.
go back to reference Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004;22:745–63.CrossRefPubMed Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004;22:745–63.CrossRefPubMed
26.
go back to reference Morris G, Maes M. A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome. Metab Brain Dis. 2013;28(4):523–40.CrossRefPubMed Morris G, Maes M. A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome. Metab Brain Dis. 2013;28(4):523–40.CrossRefPubMed
27.
go back to reference Poggi A, Carosio R, Fenoglio D, Brenci S, Murdaca G, Setti M, et al. Migration of Vδ1 and Vδ2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1–infected patients: competition by HIV-1 Tat. Blood. 2004;103(6):2205–13.CrossRefPubMed Poggi A, Carosio R, Fenoglio D, Brenci S, Murdaca G, Setti M, et al. Migration of Vδ1 and Vδ2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1–infected patients: competition by HIV-1 Tat. Blood. 2004;103(6):2205–13.CrossRefPubMed
Metadata
Title
Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients
Authors
Sharni Lee Hardcastle
Ekua Weba Brenu
Samantha Johnston
Thao Nguyen
Teilah Huth
Sandra Ramos
Donald Staines
Sonya Marshall-Gradisnik
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0653-3

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