Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis, 2017, Lidbury et al

Hutan

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https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1161-4

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.
 
These sort of things occurred with cytokines a lot, but what counts is how they subgrouped for analysis. They kept getting cytokine studies wrong, because they (the researchers) kept making assumptions that were wrong. This influenced study design and analysis.

So this is a red flag, and shows we cannot reliably cite activin B as a biomarker, but does not prove it either is or is not a biomarker.
 
The study and the workshop report reference have the same lead author. I hope to look at this later and maybe email him, but I am busy right now.

PS You can start an email by clicking on the lead author name in the .pdf.
 
Reference norms of Activin A and B (etc.) from where they were determined in Citation 8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057391/figure/F2/?report=objectonly
F2
 
From the Dec 2018 MDRN Workshop Report
An update on the activin B work:

View attachment 6187

Umm, they found activin B still differentiated people with ME/CFS from healthy controls but this time activin B concentrations were lower in the ME/CFS cohort...

That's a bit of a problem, isn't it? Am I missing something?
Thread on this follow-up work, Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning & Utility of Activin B for Defining Symptom Severity (2019) Lidbury et al.
 
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