Commonly used clinical diagnostic criteria include the Fukuda4, Canadian5, and Institute of Medicine (IOM)6 criteria. These clinical criteria are essential for accurately identifying possible cases of CFS. However, the accuracy of clinical diagnosis is improved when additional objective testing is available. In our studies of genetic forms of mitochondrial disease we developed a novel mass spectrometry-based method that allows us to measure over 500 molecules in the blood. Some people have likened these NextGen metabolomics methods to a new lens, like the Hubble telescope, that allow us to see deeper and with greater clarity into the universe of the cell than has been possible before.
In our first studies of CFS we wanted to answer 3 basic questions:
- Can NextGen Metabolomics be used to assist with the diagnosis of CFS?
- Can the chemical information provided by metabolomics be used to help with the development of treatment plans tailored to the individual?
- Does a systems analysis of the metabolic abnormalities found in CFS lead us to a better understanding of the root biology underlying the disease?
In a study conducted in collaboration with Dr. Eric Gordon, we have completed a metabolomics study of 84 subjects with chronic fatigue syndrome meeting the criteria of Fukuda, the Canadian, and the IOM. The paper describing the results has been published at PNAS (Open Access link) (PDF) (UC San Diego Press Release).
The results for this first study using our NextGen metabolomics platform are very exciting. We have been able to show that CFS has a chemical signature that can be identified using targeted plasma metabolomics. The pattern and directionality of these changes showed that CFS is a conserved, hypometabolic response to environmental stress similar to dauer, which is a hypometabolic syndrome seen in other organisms. Only about 25% of the metabolite disturbances found in each person were needed for the diagnosis of CFS. About 75% of the metabolite abnormalities were unique to the individual and could be useful in guiding personalized treatment. The finding of an objective chemical signature in CFS helps to remove diagnostic uncertainty, will help clinicians monitor individualized responses to treatment, and will facilitate multicenter clinical trials.
Learn more about the study and its implications in this Metabolomics Q&A for CFS
We are now planning the next study to validate the results of the first study in a larger population of CFS patients distributed throughout North America in collaboration with Dr. Paul Cheney. Metabolomics results will be compared with genomics in collaboration with Dr. Ron W. Davis at Stanford. If you would like to learn more about this study please reach out to us via our Contact page.
- Levine, P.H., et al. Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome. Archives of internal medicine 152, 1611-1616 (1992).
- Buchwald, D., et al. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection. Ann Intern Med 116, 103-113 (1992).
- Bell, D.S., Jordan, K. & Robinson, M. Thirteen-year follow-up of children and adolescents with chronic fatigue syndrome. Pediatrics 107, 994-998 (2001).
- Fukuda, K., et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 121, 953-959 (1994).
- Carruthers, B.M., et al. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. Journal of Chronic Fatigue Syndrome 11 (2003).
- Medicine, I.o. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Vol.http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx (The National Academies Press, Washington, DC, 2015).