Validation of biologic markers for use in research on chronic fatigue syndrome

Abstract:

Unresolved aspects of chronic fatigue syndrome can be addressed by research involving biologic markers. These may be any molecular, biochemical, physiological, or other biologic parameter obtainable from biologic specimens. The use of biologic markers in research requires their validation as dependent or independent variables. Additionally, other characteristics of markers such as reliability of assays, background level, confounding factors, interpretations, and legal and ethical implications should be considered before the use of markers in research. A checklist is provided for evaluating a biologic marker before its inclusion in research.

 

Source: Schulte PA. Validation of biologic markers for use in research on chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S87-9. http://www.ncbi.nlm.nih.gov/pubmed/2020808

 

Chronic fatigue syndrome and the diagnostic utility of antibody to Epstein-Barr virus early antigen

Abstract:

Antibody to Epstein-Barr virus (EBV) early antigen has been said to be the most specific indicator of symptomatic chronic EBV infection. We studied the clinical utility of this serologic test in the evaluation of patients with chronic fatigue.

Thirty patients with chronic fatigue and highly elevated titers of antibody to early antigen (greater than or equal to 1:160) were compared with 30 age- and sex-matched controls with no antibody to early antigen.

There were no significant differences noted between patients and controls at the initial evaluation (symptoms, physical examination, laboratory data). Follow-up information, available for 15 matched pairs, showed no differences in outcome between patients and controls. We conclude that the antibody to EBV early antigen is not helpful in the clinical evaluation of patients with chronic fatigue.

 

Source: Hellinger WC1, Smith TF, Van Scoy RE, Spitzer PG, Forgacs P, Edson RS. Chronic fatigue syndrome and the diagnostic utility of antibody to Epstein-Barr virus early antigen. JAMA. 1988 Aug 19;260(7):971-3. http://www.ncbi.nlm.nih.gov/pubmed/2840523

 

Immune Markers in Cerebrospinal Fluid Provide Insights Into the Basis for Symptoms Like “Brain Fog”

Press Release: Mailman School of Public Health, March 30, 2015. Scientists at Columbia University’s Mailman School of Public Health have identified a unique pattern of immune molecules in the cerebrospinal fluid of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that provides insights into the basis for cognitive dysfunction—frequently described by patients as “brain fog”—as well as new hope for improvements in diagnosis and treatment.

In the study published in Molecular Psychiatry, Mady Hornig, MD, and colleagues used immunoassay testing methods to measure levels of 51 immune biomarkers called cytokines in the cerebrospinal fluid of 32 people with ME/CFS for an average of seven years, 40 with multiple sclerosis, and 19 non-diseased controls. The researchers found that levels of most cytokines, including the inflammatory immune molecule interleukin 1, were depressed in individuals with ME/CFS compared with the other two groups, matching what was seen in a blood study in patients who had the disease for more than three years. One cytokine—eotaxin—was elevated in the ME/CFS and MS groups, but not in the control group.

“We now know that the same changes to the immune system that we recently reported in the blood of people with ME/CFS with long-standing disease are also present in the central nervous system,” says Dr. Hornig, professor of Epidemiology and director of translational research at the Center for Infection and Immunity at the Mailman School. “These immune differences may contribute to symptoms in both the peripheral parts of the body and the brain, from muscle weakness to brain fog.”

Implications for Diagnosis and Treatment

“Diagnosis of ME/CFS is now based on clinical criteria. Our findings offer the hope of objective diagnostic tests for disease as well as the potential for therapies that correct the imbalance in cytokine levels seen in people with ME/CFS at different stages of their disease,” adds W. Ian Lipkin, MD, John Snow Professor of Epidemiology and director of the Center for Infection and Immunity.

There is precedent for use of human monoclonal antibodies that regulate the immune response in a wide range of disorders from rheumatoid arthritis to multiple sclerosis. However, the researchers note, additional work will be needed to assess the safety and efficacy of this approach.

The study was supported by a grant from the Chronic Fatigue Initiative of the Hutchins Family Foundation and the Edward P. Evans Foundation.

Additional authors include Andrew F. Schultz, Meredith L. Eddy and Xiaoyu Che at the Mailman School; C. Gunnar Gottschalk and Daniel L. Peterson at Sierra Internal Medicine in Incline Village, NV; and Konstance K. Knox at Coppe Health Care Solutions in Waukesha, WI, and Simmaron Research in Incline Village, NV.

Journal Reference: M Hornig, G Gottschalk, D L Peterson, K K Knox, A F Schultz, M L Eddy, X Che, W I Lipkin. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome. Molecular Psychiatry, 2015; DOI: 10.1038/mp.2015.29