Whole blood gene expression in adolescent chronic fatigue syndrome: An exploratory cross-sectional study suggesting altered B cell differentiation and survival

Journal of Translational Medicine

Volumn 15, Issue 1, 2017, Pages

  Nguyen, Chinh Bkrong ^a,b   Alsøe, Lene ^a   Lindvall, Jessica M ^c   Sulheim, Dag ^d   Fagermoen, Even ^e   Winger, Anette ^f   Kaarbø, Mari ^e   Nilsen, Hilde ^a   Wyller, Vegard Bruun ^a,b  

^a AKERSHUS UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

^c STOCKHOLM UNIVERSITY   (Sweden)

^d Lillehammer County Hospital   (Norway)

^e OSLO UNIVERSITY HOSPITAL   (Norway)

^f OSLO METROPOLITAN UNIVERSITY   (Norway)

Author keywords

Adolescent; B cell differentiation; B cell survival; Chronic fatigue syndrome; Gene expression; Inflammation

Indexed keywords

C REACTIVE PROTEIN; INTERLEUKIN 1; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 6; TUMOR NECROSIS FACTOR; BIOLOGICAL MARKER; MESSENGER RNA;

ADOLESCENT; ADULT; AGE DISTRIBUTION; ANXIETY; ARTICLE; AUTONOMIC NERVOUS SYSTEM; B LYMPHOCYTE; B LYMPHOCYTE DIFFERENTIATION; CATECHOLAMINE BLOOD LEVEL; CATECHOLAMINE URINE LEVEL; CELL SURVIVAL; CELL VIABILITY; CHILD; CHRONIC FATIGUE SYNDROME; CLINICAL ARTICLE; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DEPRESSION; DOWN REGULATION; EOSINOPHIL COUNT; EXPLORATORY RESEARCH; FEMALE; GENE EXPRESSION; GENETIC ASSOCIATION; HEART RATE VARIABILITY; HUMAN; HYDROCORTISONE BLOOD LEVEL; HYDROCORTISONE URINE LEVEL; INFLAMMATION; INNATE IMMUNITY; LEUKOCYTE COUNT; MALAISE; MALE; MONOCYTE; PATHOPHYSIOLOGY; PROTEIN BLOOD LEVEL; RNA SEQUENCE; SEQUENCE ALIGNMENT; SEX DIFFERENCE; TRAIT ANXIETY; UPREGULATION; VALIDATION PROCESS; BLOOD; CASE CONTROL STUDY; CELL DIFFERENTIATION; CLUSTER ANALYSIS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; METABOLISM; PATHOLOGY; STATISTICS;

ADOLESCENT; B-LYMPHOCYTES; BIOMARKERS; CASE-CONTROL STUDIES; CELL DIFFERENTIATION; CELL SURVIVAL; CHILD; CLUSTER ANALYSIS; CROSS-SECTIONAL STUDIES; FATIGUE SYNDROME, CHRONIC; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HUMANS; MALE; RNA, MESSENGER; STATISTICS AS TOPIC;

EID: 85019058090     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/s12967-017-1201-0     Document Type: Article

References (89)

1. Institute of Medicine. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, DC: The National Academies Press; 2015.
2. Royal College of Paediatrics and Child Health. Evidence based guidelines for the management of CFS/ME (chronic fatigue syndrome/myalgic encephalopathy) in children and young adults. London: Royal College of Paediatrics and Child Health; 2004.
3. Crawley EM, Emond AM, Sterne JA. Unidentified chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a major cause of school absence: surveillance outcomes from school-based clinics. BMJ Open. 2011;1:e000252.
4. Jason LA, Bell DS, Rowe K, et al. A pediatric case definition for chronic fatigue syndrome. J Chronic Fatigue Syndr. 2006;13:1-44.
5. Nijhof SL, Maijer K, Bleijenberg G, Uiterwaal CS, Kimpen JL, van der Putte EM. Adolscent chronic fatigue syndrome: prevalence, incidence, and morbidity. Pediatrics. 2011;127:e1169-75.
6. Kennedy G, Underwood C, Belch JJ. Physical and functional impact of chronic fatigue syndrome/myalgic encephalomyelitis in childhood. Pediatrics. 2010;125:e1324-30.
7. Missen A, Hollingwort W, Eaton N, Crawley E. The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME). Child Care Health Dev. 2012;38:505-12.
8. Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012;26:24-31.
9. Klimas NG, Broderick G, Fletcher MA. Biomarkers for chronic fatigue. Brain Behav Immun. 2012;26:1202-10.
10. Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. 2009;23:327-37.
11. Fluge Ø, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Næss H, Dahl O, Nyland H, Mella O. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome: a double-blind and placebo-controlled study. PLoS ONE. 2011;6:e26358.
12. Maes M, Twisk FN, Ringel K. Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychother Psychosom. 2012;81:286-95.
13. Fletcher MA, Zeng XR, Barnes Z, Levis S, Klimas NG. Plasmas cytokines in women with chronic fatigue syndrome. J Transl Med. 2009;7:96.
14. Vollmer-Conna U, Cameron B, Pavlonic DH, Singletary K, Davenport T, Vernon S, Reeves WC, Hickie I, Wakenfield D, Lloyd AR. Postinfective fatigue syndrome is not associated with altered cytokine production. Clin Infect Dis. 2007;45:732-5.
15. Wyller VB, Sørensen Ø, Sulheim D, Fagermoen E, Ueland T, Mollnes TE. Plasma cytokine expression in adolescent chronic fatigue syndrome. Brain Behav Immun. 2015;46:80-6.
16. Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey DL, Richards SCM, Montgomery J, Baldwin DA, Kellam P, Harrison TJ, Griffin GE, Main J, Enlander D, Nutt DJ, Holgate ST. Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis. 2008;197:1171-84.
17. Zhang L, Gough J, Christmas D, Mattey DL, Richards SCM, Main K, Enlander D, Honeybourne D, Ayres JG, Nutt DJ, Kerr JR. Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. J Clin Pathol. 2010;63:156-64.
18. Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with chronic fatigue syndrome and fibromyalgia syndrome. J Intern Med. 2012;271:64-81.
19. Nijs J, Nees A, Paul L, De Kooning M, Ickmans K, Meeus M, Van Oosterwijck J. Altered immune responses to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review. Exerc Immunol Rev. 2014;20:94-116.
20. Fang H, Xie Q, Boneva R, Fostel J, Perkins R, Tong W. Gene expression profile exploration of a large dataset on chronic fatigue syndrome. Pharmacogenomics. 2006;7:429-40.
21. Gow JW, Hagan S, Herzyk P, Cannon C, Behan PO, Chaudhuri A. A gene signature for post-infectious chronic fatigue syndrome. BMC Med Genom. 2009;2:38.
22. Byrnes A, Jacks A, Dahlman-Wright K, et al. Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue: no evidence of a biomarker. PLoS ONE. 2009;4:e5805.
23. Frampton D, Kerr J, Harrison TJ, Kellam P. Assessment of a 44 gene classifier for the evaluation of chronic fatigue syndrome from peripheral blood mononuclear cell gene expression. PLoS ONE. 2011;6:e16872.
24. Fostel J, Boneva R, Lloyd A. Exploration of the gene expression correlates of chronic unexplained fatigue using factor analyses. Pharmacogenomics. 2006;7:441-54.
25. Galbraith S, Cameron B, Li H, Lau D, Vollmer-Conna U, Lloyd AR. Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections. J Infect Dis. 2011;204:1632-40.
26. Martínez-Martínez LA, Mora T, Varqas A, Fuentes-Iniestra M, Martínez-Lavin M. Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies. J Clin Rhematol. 2014;20:146-50.
27. Wyller VB, Barbieri R, Saul P. Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress. Eur J Appl Physiol. 2011;111:497-502.
28. Wyller VB, Barbieri R, Thaulow E, Saul JP. Enhanced vagal withdrawal during mild orthostatic stress in adolescents with chronic fatigue. Ann Noninvasive Electrocardiol. 2008;13:67-73.
29. Wyller VB, Due R, Saul JP, Amlie JP, Thaulow E. Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls. Am J Cardiol. 2007;99:997-1001.
30. Papadopoulos AS, Cleare AJ. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011;27:22-32.
31. Segal TY, Hindmarsh PC, Viner RM. Disturbed adrenal function in adolescents with chronic fatigue syndrome. J Pediatr Endocrinol Metab. 2005;18:295-301.
32. Wyller VB, Vitelli V, Sulheim D, Fagermoen E, Winger A, Godang K, Bollerslev J. Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. J Transl Med. 2016;14:121.
33. Zen M, Canova M, Campana C, Bettio S, Nalotto L, Rampudda M, Ramonda R, Iaccarino L, Doria A. The kaleidoscope of glucocorticoid effects on immune system. Autoimmun Rev. 2011;10:305-10.
34. Andersson U, Tracey KJ. Neural reflexes in inflammation and immunity. J Exp Med. 2012;209:1057-68.
35. Padro CJ, Sanders VM. Neuroendocrine regulation of inflammation. Semin Immunol. 2014;26:357-68.
36. Thayer JF, Sternberg EM. Neural aspects of immunomodulation: focus on the vagus nerve. Brain Behav Immun. 2010;24:1223-8.
37. Wyller VB, Malterud K, Eriksen HR. Can sustained arousal explain chronic fatigue syndrome? Behav Brain Funct. 2009;5:10.
38. Cividjian A, Toader E, Wesseling KH, Karemaker JM, McAllen R, Quintin L. Effect of clonidine on cardiac baroreflex delay in humans and rats. Am J Physiol Regul Integr Comp Physiol. 2011;300:949-57.
39. Sulheim D, Fargermoen E, Winger A, Andersen AM, Godang K, Müller F, Rowe PC, Saul JP, Skovlund E, Øie MG, Wyller VB. Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized controlled trial. JAMA Pediatr. 2014;168:351-60.
40. National Institute for Health and Clinical Excellence: chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy). Diagnosis and management of CFS/ME in adults and children. London: NICE clinical guideline, 2007, no. 53.
41. Babraham Bioinformatics, Babraham Institute, Cambridge, UK. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/. Accessed 23 Feb 2017.
42. Hannon Lab, Cold Spring Harbor Laboratory, New York, USA. http://www.hannonlab.cshl.edu. Accessed 23 Feb 2017.
43. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15-21.
44. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5:R80.
45. Liao Y, Smyth GK, Shi W. The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 2013;41:e108.
46. Risso D, Nqai J, Speed TP, Dudoit S. Normalization of RNA-seq data using factor analyses of control genes or samples. Nat Biotechnol. 2014;32:896-902.
47. Anders S, McCarthy DJ, Chen Y, Okoniewsky M, Smyth GK, Huber W, Robinson MD. Count-based differential expression analysis of RNA sequencing data using R and bioconductor. Nat Protoc. 2013;8:1765-86.
48. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
49. HumanMine Database, University of Cambridge, UK. http://www.humanmine.org. Accessed 23 Feb 2017.
50. Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J. ClueGO: a cytoscape plug-into decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25:1091-3.
51. Aspler AL, Bolshin C, Vernon SD, Broderick G. Evidence of inflammatory immune signaling in chronic fatigue syndrome: a pilot study of gene expression in peripheral blood. Behav Brain Funct. 2008;4:44.
52. Preininger M, Arafat D, Kim J, Nath AP, Idaghdour Y, Brigham KL, Gibson G. Blood-informative transcripts define nine common axes of peripheral blood gene expression. PLoS Genet. 2013;9:e1003362.
53. Fagermoen E, Sulheim D, Winger A, Andersen AM, Gjerstad J, Godang K, Rowe PC, Saul JP, Skovlund E, Wyller VB. Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue syndrome: a randomized controlled trial. BMC Pediatr. 2015;15:117.
54. Task force of the European society of cardiology, and the North American society of pacing electrophysiology. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Circulation. 1996;93:1043-65.
55. Chalder T, Berelowitz G, Pawlikowska T, et al. Development of a fatigue scale. J Psychosom Res. 1993;37:147-53.
56. Daviss WB, Birmaher B, Melhem NA, Axelson DA, Michaels SM, Brent DA. Criterion validity of the Mood and Feelings Questionnaire for depressive episodes in clinic and non-clinic subjects. J Child Psychol Psychiatry. 2006;47:927-34.
57. Kendall PC, Finch AJ Jr, Auerback SM, Hooke JF, Mikulka PJ. The state-trait anxiety inventory: a systematic evaluation. J Consult Clin Psychol. 1976;44:406-12.
58. Grant PM, Ryan CG, Tigbe WW, Granat MH. The validation of a novel activity monitor in the measurement of posture and motion during everyday activities. Br J Sports Med. 2006;40:992-7.
59. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008;5:621-8.
60. Ninq S, Pagano JS. The A20 deubiquitinase activity negatively regulates LPM1 activation of IRF7. J Virol. 2010;84:6130-8.
61. Griffith J, et al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell. 2004;13:169-78.
62. Vilagos B, et al. Essential role of EBF1 in the generation and function of distinct mature B cell types. J Exp Med. 2012;209:775-92.
63. Chu PG, Arber DA. CD79: a review. Appl Immunohistochem Mol Morphol. 2001;9:97-106.
64. Pereira JP, et al. Finding the right niche: B-cell migration in the early phases of T-dependent antibody responses. Int Immunol. 2010;22:413-9.
65. Kayagaki N, et al. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-ΚB2. Immunity. 2002;17:515-24.
66. Stenglein MD, et al. APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nat Struct Mol Biol. 2010;17:222-9.
67. Dong B, et al. Phospholipid scramblase 1 potentiates the antiviral activity of interferon. J Virol. 2004;78:8983-93.
68. Blaszczyk K, Nowicka H, Kostyrko K, Antonczyk A, Wesoly J, Bluyssen HA. The unique role of STAT2 in constitutive and INF-induced transcription and antiviral responses. Cytokine Growth Factor Rev. 2016;29:71-81.
69. Cervantes JL, et al. TLR8: the forgotten relative revindicated. Cell Mol Immunol. 2012;9:434-8.
70. Sun Q, Scott MJ. Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. J Leukoc Biol. 2016;100:961-7.
71. Welte S, Kuttruff S, Waldhauer I, Steinle A. Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction. Nat Immunol. 2006;7:1334-42.
72. Bender AT, Beavo JA. PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte. Proc Natl Acad Sci USA. 2006;103:460-5.
73. Lunde S, Kristoffersen EK, Sapkota D, Risa K, Dahl O, Bruland O, Mella O, Fluge Ø. Serum BAFF and APRIL levels, T-lymphocyte subsets, and immunoglobulins after B-cell depletion using the monoclonal anti-CD20 antibody rituximab in myalgic encephalopathy/chronic fatigue syndrome. PLoS ONE. 2016;11:e0161226.
74. Brenu EW, Huth TK, Hardcastle SL, Fuller K, Kaur M, Johnston S, Ramos SB, Staines DR, Marshall-Gradisnik SM. Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis. Int Immunol. 2014;26:233-42.
75. Bradley AS, Ford B, Bansal AS. Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls. Clin Exp Immunol. 2013;172:73.
76. Mensah F, Bansal A, Berkovitz S, Sharma A, Reddy V, Leandro MJ, Cambridge G. Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study. Clin Exp Immunol. 2016;184:237-47.
77. Guenther S, Loebel M, Mooslechner AA, Knops M, Hanitsch LG, Grabowski P, Wittke K, Meisel C, Unterwalder N, Volk HD, Scheibenbogen C. Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome. Hum Immunol. 2015;76:729-35.
78. Levit-Zerdoun E, Becker M, Pohlmeyer R, Wilhelm I, Maity PC, Rajewsky K, Reth M, Hobeika E. Survival of Igα-deficient mature B cells requires BAFF-R function. J Immunol. 2016;196:2348-60.
79. Morris G, Berk M, Walder K, Maes M. The putative role of viruses, bacteria, and chronic fungal biotoxin exposure in the genesis of intractable fatigue accompanied by cognitive and physical disability. Mol Neurobiol. 2016;53:2550-71.
80. Katz BZ, Shiraishi Y, Mears CJ, et al. Chronic fatigue syndrome after infectious mononucleosis in adolescents. Pediatrics. 2009;124:189-93.
81. Thorley-Lawson DA. EBV persistence-introducing the virus. Curr Top Microbiol Immunol. 2015;390:151-209.
82. Loebel M, Strohschein K, Gianni C, Koelsch U, Bauer S, Doebis C, Thomas S, Unterwalder N, von Baehr V, Reinke P, Knops M, Hanitsch LG, Meisel C, Volk HD, Schneibenbogen C. Deficient EBV-specific B- and T-cell responses in patients with chronic fatigue syndrome. PLoS ONE. 2014;9:e85387.
83. Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA. A formal analysis of cytokine networks in chronic fatigue syndrome. Brain Behav Immun. 2010;24:1209-17.
84. Chacko A, Staines DR, Johnston SC, Marshall-Gradisnik SM. Dysregulation of protein kinase gene expression in NK cells from chronic fatigue syndrome/myalgic encephalomyelitis patients. Gene Regul Syst Biol. 2016;10:85-93.
85. Nijhof SL, Rutten JM, Uiterwaal CS, Bleijenberg G, Kimpen JL, Putte EM. The role of hypocortisolism in chronic fatigue syndrome. Psychoneuroendocrinology. 2014;42:199-206.
86. Cole SW. Human social genomics. PLoS Genet. 2014;10:e1004601.
87. Cole SW, Capitano JP, Chun K, Arevalo JM, Ma J, Cacioppo JT. Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. Proc Natl Acad Sci USA. 2015;112:15142-7.
88. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994;121:953-9.
89. Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, Lerner AM, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J Chronic Fatigue Syndr. 2003;11:7-11.