Reprinted & reproduced with the permission of the

University of Miami - February 2009

Battling & Discovering Chronic Fatigue Syndrome

The E.M. Papper Laboratory of Clinical Immunology in the Division of Laboratories offers expert assessments of immune function to the medical community. The laboratory serves as a clinical reference laboratory for physicians as well as a research core facility. The laboratory, directed

by Mary Ann Fletcher, Ph.D., and Nancy Klimas, M.D., serves as the core laboratory resource for University of Miami research into chronic fatigue syndrome and related fatiguing illnesses. It also offers clinical and research assays to many University of Miami clinical and basic science researchers, as well as to hospitals and pharmaceutical companies.

Mary Ann Fletcher, Ph.D.

Division Chief/Professor

Professor

Nancy G. Klimas, M.D.

For the estimated four million Americans with chronic fatigue syndrome (CFS)—a debilitating disease characterized by severe, incapacitating fatigue that doesn’t improve with rest and can actually worsen with physical or mental activity—just getting through the day can be a challenge. Among these estimates are veterans with Gulf War Illness (GWI) who report symptoms identical to CFS. That’s because individuals with CFS and GWI not only experience severe fatigue, they often complain of muscle and body aches, have difficulty concentrating, and therefore perform poorly on the job.

After more than two decades of research into this baffling and complex disorder, Mary Ann Fletcher, Ph.D., and Nancy Klimas, M.D., co-directors of the Emanuel M. Papper Laboratory of Clinical Immunology in the Division of Laboratories at the Miller School of Medicine, are shedding light on the biological and physiological mechanisms of this complex disorder to develop effective treatments for patients.  Current efforts are looking at better ways of characterizing this elusive disease. Scientists point to several key areas: infectious agents such as viruses, problems with hormone regulation in the body’s endocrine system, disturbances in the autonomic regulation of blood pressure and pulse, and immunologic dysfunction.

As many as 80 percent of CFS sufferers go undiagnosed, since many other illnesses share the same symptoms of the disorder.

The division’s ongoing research into CFS and GWI has led to many pivotal discoveries. One important finding made by Drs. Fletcher and Klimas is that natural killer cell (NKC) function, an essential part of innate immunity and one of the body’s major defenses against viruses, is a common immune abnormality in all three syndromes. Lower NKC function decreases the body’s ability to fight new viral infection; it’s also pivotal in keeping old virus infections at bay (in a latent form).  One goal for researchers in the division is to define objective markers, which are proteins that can be detected in the blood and used to determine whether an individual is at risk for developing a disease. Currently, a CFS diagnosis is made solely on clinically grounds, since no markers associated with the disease have been found. Identifying such markers will enable clinicians to effectively diagnose CFS, follow the progress of the disease, and monitor the effects of therapeutic approaches. CFS is an umbrella term, covering several subgroups.  Drs. Klimas and Fletcher believe they will identify biochemical and immunologic markers for CFS that will be used to diagnose the illness, help put the patient in the right subgroup, and predict recovery or relapse.

The Gulf War Illness Research Study is a large genomics study that is analyzing the role of gene expression patterns in the symptoms of Gulf War Illness compared to CFS.

The Gulf War Illness Research Study, being conducted in conjunction with the Centers for Disease Control (CDC) and funded by the Veteran’s Administration and the Department of Defense, is a large genomics study that is analyzing the role of gene expression patterns in the symptoms of Gulf War Illness compared to CFS. By using a technique called gene expression by microarray, researchers are examining patients’ gene expression before, during, and after exercise. It’s hoped that those genes that are expressed can be singled out, allowing researchers to know what proteins those genes code for so that they can then identify biomarkersfor the disease.

The “Good Day/Bad Study" also seeks to find biomarkers that can be used to predict partial relapse and/or partial recovery in CFS patients. Drs. Fletcher and Klimas, along with their team, will examine 150 patients over a five-year period by drawing their blood on “good” days (when individuals feel relatively healthy and active) as well as on “bad” days (when patients cannot get out of bed due to severe fatigue) and compare it to that of healthy individuals.

A pilot study originally funded by the CFIDS Association of America (CFIDS stands for chronic fatigue and immune dysfunction syndrome), which was then spun into an NIH grant, is helping researchers study the role of two specific biomarkers in the development of CFS—neuropeptide Y (NPY) and dipeptidylpeptidase (CD26).These peptides, formed from amino acids, regulate many physiological and disease processes in the cardiorespiratory, immune, nervous, and endocrine systems. NPY is an important neurotransmitter produced by sympathetic nerve endings in response to stress and is elevated in CFS. Meanwhile, low CD26 will produce elevated levels of the peptide, resulting in immune dysfunction, and ultimately, the symptoms of CFS. Dr. Klimas presented the findings of this research to the Academy of Behavioral Medicine Research in June 2008.