E2 ModeratePreliminaryPEM unclearCross-SectionalPeer-reviewedReviewed
Evidence of a Novel Mitochondrial Signature in Systemic Sclerosis Patients with Chronic Fatigue Syndrome.
van Eeden, Charmaine, Redmond, Desiree, Mohazab, Naima et al. · International journal of molecular sciences · 2023 · DOI
Quick Summary
This study looked at people with a connective tissue disease called systemic sclerosis who also experience severe fatigue (ME/CFS symptoms). Researchers found that fatigued patients had different patterns in how their cells' energy-producing structures (mitochondria) work compared to non-fatigued patients. These differences involved specific genes related to energy production, suggesting that measuring these genes might help doctors identify which systemic sclerosis patients have ME/CFS.
Why It Matters
This research provides the first potential biomarker signature to distinguish ME/CFS in systemic sclerosis patients, addressing a significant gap since no validated biomarkers currently exist for ME/CFS. If validated, these mitochondrial markers could enable earlier identification of fatigued patients and potentially predict more severe disease outcomes, improving clinical management and prognosis.
Observed Findings
- ME/CFS-related symptoms were common in early-stage limited cutaneous systemic sclerosis patients.
- Fatigued SSc patients showed reduced expression of mitochondrial genes ND4 and CyB compared to non-fatigued patients.
- Fatigued SSc patients showed increased expression of mitochondrial gene Cox7C compared to non-fatigued patients.
- ND4 and CyB expression levels correlated with markers of systemic sclerosis disease severity.
Inferred Conclusions
- An altered mitochondrial electron transport chain gene expression signature distinguishes ME/CFS-affected from non-fatigued systemic sclerosis patients.
- Mitochondrial gene expression patterns may serve as potential biomarkers for identifying ME/CFS in systemic sclerosis.
- Mitochondrial dysfunction may be associated with both fatigue and disease severity progression in systemic sclerosis.
Remaining Questions
- Does this mitochondrial signature predict progression to more severe systemic sclerosis disease outcomes prospectively?
- Are the identified mitochondrial changes functional markers of actual energy production impairment, or merely associated transcriptional changes?
- Can this mitochondrial signature be used to identify ME/CFS in other rheumatic diseases or in primary ME/CFS without systemic sclerosis?
What This Study Does Not Prove
This study does not prove that mitochondrial dysfunction causes ME/CFS or fatigue—it only shows an association. The cross-sectional design cannot establish whether the mitochondrial changes precede fatigue development or result from it. These findings are specific to systemic sclerosis patients and may not apply to ME/CFS in other conditions or in primary ME/CFS without underlying rheumatic disease.
Tags
Symptom:Fatigue
Biomarker:Gene ExpressionBlood Biomarker
Method Flag:PEM Not DefinedSmall SampleExploratory OnlyMixed CohortWeak Case Definition
Phenotype:Gradual Onset
Metadata
- DOI
- 10.3390/ijms241512057
- PMID
- 37569433
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 12 April 2026
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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