Abstract

Chronic fatigue syndrome (CFS) remains an incompletely characterized illness, in part due to controversy regarding its definition, biological basis, and diagnosis.

Biomarkers are objective measures that may lead to improvements in our understanding of CFS by providing a more coherent and consistent approach to study, diagnosis, and treatment of the illness. Such metrics may allow us to distinguish between CFS subtypes – each defined by characteristic biomarkers – currently conflated under the single, heterogeneous condition of CFS. These delineations, in turn, may guide more granular, focused, and targeted treatment strategies based on more precise characterizations of the illness.

Here, we review potential CFS biomarkers related to neurological and immunological components of the illness. We discuss how these biomarkers may be used to move the field of CFS forward, emphasizing clinical utility and potential routes of future research.

Conclusion

Recent research efforts have resulted in recommendations for minimal elements in research papers on CFS.[3] Research and clinical management of CFS will benefit from a more objective system of characterization, just as the CP/CPPS benefited from the DABBEC phenotyping method.[11] Based on the current state of research on the topic, biomarkers offer a strong potential for characterizing CFS subgroups in terms of clinical phenotypes, endophenotypes, prognosis, and response to therapy.

We have categorized reliable but disparate markers of the disease into distinct categories that can be used to delineate etiologically distinct subtypes of CFS, which can, in turn, be used to develop a more nuanced definition of the disease and more customized approaches to treatment. Of course, this proposed framework cannot be utilized effectively without remaining amenable to future research developments.

First, the criteria for using these biomarkers in diagnosis must be defined, along with the phenotypes that they accompany. Then, the reliability and effectiveness of these biomarkers must be tested for diagnostic and/or prognostic capacity, to propel our understanding and treatment of disease forward.

Moreover, if biomarkers are going to be practically useful to assist in diagnosis, CFS patients with other comorbidities such as multiple sclerosis, lupus, depression, and other comorbid disorders with CFS must be included in these studies (“ill controls” or comparison groups) to allow evaluation of the specificity of the proposed biomarkers for CFS.

Second, as novel biomarkers are discovered and the biological underpinnings of CFS are elucidated, these contributions to the existing body of knowledge must be incorporated into the proposed framework. Only by continuously evolving with the research on which it depends can this proposed model accurately reflect the true nature of the disease. Hopefully, as future studies are performed and validated, the current model will retain its flexibility and will allow incorporation of new knowledge into the working framework of CFS. It is only by developing a more nuanced and granular framework for CFS – one that can be shared by researchers and clinicians alike – that our knowledge of the disease, and of potential treatments, can progress.

Chronic fatigue syndrome: the current status and future potentials of emerging biomarkers by David B. Fischera, Arsani H. Williama, Adam C. Straussab, Elizabeth R. Ungerc, Leonard A. Jason, Gailen D. Marshall Jr & Jordan D. Dimitrakofffg in Fatigue: Biomedicine, Health & Behavior Volume 2, Issue 2, 2014