E2 ModeratePreliminaryPEM not requiredCross-SectionalPeer-reviewedReviewed
Standard · 3 min
Pitfalls in cytokine measurements - Plasma TGF-β1 in chronic fatigue syndrome.
Roerink, M E, van der Schaaf, M E, Hawinkels, L J A C et al. · The Netherlands journal of medicine · 2018
Quick Summary
This study measured a protein called TGF-β1 in the blood of ME/CFS patients compared to healthy people. Previous research suggested this protein was elevated in ME/CFS, but the researchers found that how blood samples are processed in the lab—specifically how fast they spin them—dramatically affects the results. When they carefully controlled this process, they found no actual difference in TGF-β1 levels between patients and healthy controls.
Why It Matters
This study is important because it challenges a previously reported biomarker finding in ME/CFS and demonstrates how technical laboratory factors can create false positive results. For patients and researchers, it underscores the need for rigorous standardization in biological studies of ME/CFS—ensuring that apparent disease findings are genuine rather than artifacts of measurement procedures.
Observed Findings
No significant difference in TGF-β1 concentrations between CFS patients and healthy controls within either cohort
Large discrepancy in TGF-β1 levels between the two cohorts
Centrifugation at lower g-force (1361 g) caused significantly higher platelet activation, reflected by elevated P-selectin concentrations (p<0.0001)
Strong correlation between TGF-β1 and P-selectin concentrations (r=0.79, p<0.0001)
Inferred Conclusions
Previously reported elevated TGF-β1 in CFS may be a pre-analytical artifact caused by inadequate control of centrifugation procedures
Platelet activation during sample processing significantly influences measured TGF-β1 concentrations
Standardization and careful control of pre-analytical procedures are essential for valid cytokine measurements in CFS research
No evidence supports genuine elevation of TGF-β1 as a biomarker of CFS when proper methodology is employed
Remaining Questions
How many other published CFS biomarker studies may have been affected by similar pre-analytical artifacts?
Do other cytokines show the same sensitivity to centrifugation parameters, and should all future CFS studies adopt standardized protocols?
What This Study Does Not Prove
This study does not prove that TGF-β1 is never abnormal in ME/CFS—only that careful measurement under these specific conditions found no difference. It also does not address whether other cytokines or biomarkers may still be abnormal in ME/CFS. The study examined only female patients, so findings may not generalize to male patients.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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