title: Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.|The National Centre for Epidemiology and Public Health, The Research School of Population Health, ANU, Canberra, ACT, 2601, Australia. brett.lidbury@anu.edu.au.
authors.forename: Brett A
authors.identifier: 0000-0003-2211-989X
authors.initials: BA
authors.lastname: Lidbury
authors.affiliation: Paranta Biosciences Limited, Caulfield North, VIC, 3161, Australia.
authors.forename: Badia
authors.initials: B
authors.lastname: Kita
authors.affiliation: CFS Discovery, Donvale Medical Specialist Centre, Donvale, VIC, 3111, Australia.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Lewis
authors.affiliation: The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Hayward
authors.affiliation: Centre for Proteins and Peptides, School of Life Sciences, Oxford Brookes University, Headington, Oxford, OX3 0BP, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Ludlow
authors.affiliation: The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hedger
authors.affiliation: The Hudson Medical Research Institute, Monash University, Clayton, VIC, 3168, Australia.|Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, 3168, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: de Kretser
mesh_terms: D028341:Activins / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015673:Fatigue Syndrome, Chronic / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D038681:Follistatin / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; D038681:Follistatin; C422405:activin A; C044147:activin B; D028341:Activins
keywords: Activins; Biomarker; Chronic fatigue syndrome (CFS); Diagnosis; Myalgic encephalomyelitis (ME)