Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study.

Brett A Lidbury, Badia Kita, Donald P Lewis, Susan Hayward, Helen Ludlow, Mark P Hedger, David M de Kretser
Author Information
  1. Brett A Lidbury: Pattern Recognition and Pathology, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia. brett.lidbury@anu.edu.au. ORCID
  2. Badia Kita: Paranta Biosciences Limited, Caulfield North, VIC, 3161, Australia.
  3. Donald P Lewis: CFS Discovery, Donvale Medical Specialist Centre, Donvale, VIC, 3111, Australia.
  4. Susan Hayward: The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia.
  5. Helen Ludlow: Centre for Proteins and Peptides, School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK.
  6. Mark P Hedger: The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia.
  7. David M de Kretser: The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia.

Abstract

BACKGROUND: Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available.
METHODS: A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted. Comparisons with a previously defined activin reference population were also performed. For the total study cohort the age range was 18-65 years with a female: male participant ratio of greater than 3:1. All participants were assessed via a primary care community clinic. Blood samples were collected for pathology testing after physical examination and orthostatic intolerance assessment. Cytokines, activin A, activin B and follistatin were also measured in sera from these samples. All data were compared between the CFS/ME and control cohorts, with the activins and follistatin also compared with previously defined reference intervals.
RESULTS: Serum activin B levels for CFS/ME participants were significantly elevated when compared to the study controls, as well as the established reference interval. Serum activin A and follistatin were within their normal ranges. All routine and special pathology markers were within the normal laboratory reference intervals for the total study cohort, with no significant differences detected between CFS/ME and control groups. Also, no significant differences were detected for IL-2, IL-4, IL-6, IL-10, IL-17A, TNF or IFN-gamma.
CONCLUSION: Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.

Keywords

References

  1. Transplant Direct. 2016 Jun 06;2(7):e87 [PMID: 27830181]
  2. FASEB J. 2014 Apr;28(4):1711-23 [PMID: 24378873]
  3. Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16239-44 [PMID: 17911255]
  4. Mol Ther. 2015 Mar;23(3):434-44 [PMID: 25399825]
  5. Sci Signal. 2016 Feb 16;9(415):ra19 [PMID: 26884601]
  6. Clin Vaccine Immunol. 2013 Nov;20(11):1736-42 [PMID: 24027260]
  7. Clin Endocrinol (Oxf). 2009 Dec;71(6):867-73 [PMID: 19486020]
  8. Ann Intern Med. 1994 Dec 15;121(12):953-9 [PMID: 7978722]
  9. J Clin Immunol. 1997 Mar;17(2):160-6 [PMID: 9083892]
  10. J Immunol. 1995 Aug 1;155(3):1066-73 [PMID: 7636180]
  11. Blood. 2012 Jul 12;120(2):431-9 [PMID: 22611157]
  12. Cancer. 1994 May 1;73(9):2275-9 [PMID: 7513247]
  13. J Psychosom Res. 2003 Aug;55(2):79-90 [PMID: 12932505]
  14. Muscle Nerve. 2009 Mar;39(3):283-96 [PMID: 19208403]
  15. Cytokine. 1991 Jul;3(4):292-8 [PMID: 1873478]
  16. Brain Behav Immun. 2012 Mar;26(3):401-6 [PMID: 22306456]
  17. Mediators Inflamm. 2015;2015:929720 [PMID: 25834308]
  18. Crit Care. 2013 Oct 31;17(5):R263 [PMID: 24172607]
  19. J Intern Med. 2014 Apr;275(4):409-17 [PMID: 24206536]
  20. Eur J Immunol. 2015 Jun;45(6):1783-93 [PMID: 25773885]
  21. Cytokine Growth Factor Rev. 2013 Jun;24(3):285-95 [PMID: 23541927]
  22. Hum Reprod. 1999 Mar;14(3):827-32 [PMID: 10221721]
  23. Arch Intern Med. 1999 Oct 11;159(18):2129-37 [PMID: 10527290]
  24. Diabetes Care. 1996 Oct;19(10):1113-7 [PMID: 8886558]
  25. J Intern Med. 2011 Oct;270(4):327-38 [PMID: 21777306]
  26. Clin Exp Immunol. 2004 Feb;135(2):294-302 [PMID: 14738459]
  27. J Clin Microbiol. 1990 Jun;28(6):1403-10 [PMID: 2166084]
  28. BMJ Open. 2014 Feb 07;4(2):e003973 [PMID: 24508851]
  29. JAMA. 2015 Mar 17;313(11):1101-2 [PMID: 25668027]
  30. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):133-45 [PMID: 10708961]
  31. J Endocrinol. 1996 Feb;148(2):267-79 [PMID: 8699141]
  32. J Transl Med. 2013 Apr 09;11:93 [PMID: 23570606]
  33. PLoS One. 2010 May 25;5(5):e10817 [PMID: 20520837]

MeSH Term

Activins
Adult
Aged
Biomarkers
Case-Control Studies
Cohort Studies
Cross-Sectional Studies
Fatigue Syndrome, Chronic
Female
Follistatin
Humans
Male
Middle Aged
ROC Curve
Young Adult

Chemicals

Biomarkers
Follistatin
activin A
activin B
Activins

Word Cloud

Created with Highcharts 10.0.0CFS/MEactivinstudyfatiguereferenceBencephalomyelitissymptomspatientsalsofollistatincomparedlevelsnormalserumbiomarkerschronicsyndrome/myalgiccontrolspreviouslydefinedtotalcohortparticipantssamplespathologycontrolactivinsintervalsSerumwithinsignificantdifferencesdetectednovelBACKGROUND:Investigationsfamilyproteinsdiseasecomplexwide-rangingfeaturingpersistent6 monthslongerparticularlypostexertiondefinitiveavailableMETHODS:cross-sectionalobservationalfulfilling2003CanadianConsensusCriteriaparallelhealthynon-fatiguedconductedComparisonspopulationperformedagerange18-65 yearsfemale:maleparticipantratiogreater3:1assessedviaprimarycarecommunityclinicBloodcollectedtestingphysicalexaminationorthostaticintoleranceassessmentCytokinesmeasuredseradatacohortsRESULTS:significantlyelevatedwellestablishedintervalrangesroutinespecialmarkerslaboratorygroupsAlsoIL-2IL-4IL-6IL-10IL-17ATNFIFN-gammaCONCLUSION:ElevatedtogetheridentifieddiagnosticthusprovidingbasedtestmultiplephysiologicalrolescapturediversearrayexperiencedActivinbiomarkerdiagnosis:crosssectionalActivinsBiomarkerChronicsyndromeCFSDiagnosisMyalgicME

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