Biomarker Studies Summary
| Biomarker | Measurement | Finding | Clinical Utility | Validation Status |
|---|---|---|---|---|
| 2-Day CPET | VO2max Day 1 vs Day 2 | 25% reduction Day 2 in ME/CFS (Lim et al. 2020) | Objective PEM documentation; disability assessment | VALIDATED (replicated) |
| WASF3 protein | Muscle biopsy immunoblot | Elevated in ME/CFS; inverse correlation with Complex IV (Wang et al. 2023) | Research tool; potential treatment target | PRELIMINARY (n=14; needs replication) |
| NK cell cytotoxicity | Flow cytometry; cytotoxic assay | Reduced across multiple studies (Bulbule et al. 2024) | Immune dysfunction marker | MODERATE (consistent but variable) |
| Viral serology | PCR, immunostaining | Enterovirus in 82% stomach biopsies (Chia 2005); multiple viral associations (Hwang et al. 2023) | Subset identification (viral-onset) | MODERATE (specialized techniques) |
| Tryptophan-kynurenine | Plasma metabolomics | IDO metabolic trap (Phair, Davis, and Kashi 2019) | Potential treatment stratification | HYPOTHESIS (needs validation) |
References
Bulbule, Sarojini, Carl Gunnar Gottschalk, Molly E. Drosen, Daniel Peterson, Leggy A. Arnold, and Avik Roy. 2024. “Dysregulation of Tetrahydrobiopterin Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Pentose Phosphate Pathway.” Journal of Central Nervous System Disease 16: 11795735241271675. https://doi.org/10.1177/11795735241271675.
Chia, John K. S. 2005. “The Role of Enterovirus in Chronic Fatigue Syndrome.” Journal of Clinical Pathology 58 (11): 1126–32. https://doi.org/10.1136/jcp.2004.020255.
Lim, Eun-Jin, Eun-Bum Kang, Eun-Su Jang, and Chang-Gue Son. 2020. “Systematic Review of the Two-Day Cardiopulmonary Exercise Test as an Objective Assessment Tool for Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” Journal of Clinical Medicine 9 (12): 4040. https://doi.org/10.3390/jcm9124040.
Phair, Robert D., Ronald W. Davis, and Alex A. Kashi. 2019. “The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS.” Diagnostics 9 (3): 82. https://doi.org/10.3390/diagnostics9030082.
Wang, Ping-yuan, Jin Ma, Young-Chae Kim, et al. 2023. “WASF3 Disrupts Mitochondrial Respiration and May Mediate Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” Proceedings of the National Academy of Sciences 120 (34): e2302738120. https://doi.org/10.1073/pnas.2302738120.