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, Brett A Lidbury, Badia Kita, Donald P Lewis, Susan Hayward, Helen Ludlow, Mark P Hedger, David M de Kretser

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: Activins; Biomarker; Chronic fatigue syndrome (CFS); Diagnosis; Myalgic encephalomyelitis (ME).

Figures

Fig. 1
Fig. 1
Mean serum concentrations of a activin A, b activin B and c follistatin levels in study participants diagnosed with chronic fatigue syndrome (CFS/ME), compared to a study control group comprising healthy participants (study controls). d Ratio of activin B to follistatin levels (ActB:FST). Data are presented as mean ± SEM
Fig. 2
Fig. 2
Receiver Operating Curves (ROC) for a activin B, b activin A, c follistatin and d interleukin 10 (IL-10), for separating CFS/ME participants from healthy study controls recruited at the same time. The blue line represents the cytokine and the green line the 50% threshold of Sensitivity versus 1–Specificity for the protein detected in the CFS/ME or control serum
Fig. 3
Fig. 3
Mean serum concentrations of a activin A, b activin B and c follistatin levels in study participants diagnosed with chronic fatigue syndrome (CFS/ME) compared to activin/follistatin data from a reference population. Ratio of d activin B to follistatin levels (ActB:FST), e activin A to follistatin levels (ActA:FST) and f Ratio of activin B to activin A (ActB:ActA). Data are presented as mean ± SEM

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