Potential diagnostic method to identify subset of patients with chronic fatigue syndrome

Published on November 15, 2012 at 4:02 AM · No Comments

For the first time, researchers have landed on a potential diagnostic method to identify at least a subset of patients with chronic fatigue syndrome (CFS), a complex disorder with no known definitive cause or cure.

In a pilot study of six patients, scientists detected specific antibodies linked to latent Epstein-Barr virus reactivation in blood samples from people who had experienced classic CFS symptoms and responded to antiviral treatment. Control blood samples from 20 healthy people showed no such antibodies.

The research team, led by scientists from Ohio State University and Oakland University William Beaumont School of Medicine, acknowledges that the number of patients is small. But the researchers say the study's power rests in their access to 16 months of blood samples for each patient - a collection allowing for an unprecedented longitudinal look at CFS.

The researchers plan to move forward with development of a clinical laboratory test that can detect these antibodies in blood samples.

The study is published in the Nov. 14 issue of the journal PLOS ONE.

The Epstein-Barr virus is a human herpes virus that causes infectious mononucleosis and several different types of tumors. An estimated 95 percent of Americans have been infected with the virus by adulthood, according to the Centers for Disease Control and Prevention (CDC), but fewer than half have experienced an active illness. Once a person is infected, the virus remains dormant in the body, and can be reactivated without causing symptoms of illness.

In these six patients, the study suggests that a latent Epstein-Barr virus had begun to reactivate, but that the newly awakened virus never reached its full potential to take over its host cells. That partial reactivation advanced enough to generate at least two viral proteins, DNA polymerase and dUTPase, and these patients produced antibodies specifically designed to identify and neutralize those proteins for more than a year.

The scientists theorize that even in the absence of a complete active infection, these viral proteins' ability to induce inflammatory chemical signals causes enough immune system chaos to lead to CFS. The disorder's main symptom is profound fatigue for at least six months that does not improve with rest, and is accompanied by problems that can include weakness, muscle pain, impaired memory and depression. Because the illness mimics many other disorders, diagnosis is difficult. An estimated 1 million Americans have CFS, but experts believe only 20 percent are diagnosed.

The study's senior researchers agree that the work should be repeated in more patients "to confirm that these observations are real," said virologist Ron Glaser, director of the Institute for Behavioral Medicine Research at Ohio State and a co-author of the study. "But finally, after more than 20 years, this is at least something to go on."

Glaser's primary collaborators on this work are Marshall Williams, professor of molecular virology, immunology and medical genetics at Ohio State, and A. Martin Lerner, a professor of internal medicine at Oakland University William Beaumont School of Medicine.

Ohio State and Lerner's private practice, CFS LLC, have applied for a patent for the diagnostic method.

Glaser and Williams first published a paper in 1988 suggesting that these two viral proteins associated with partially reactivated Epstein-Barr virus could function as biomarkers for certain illnesses, including CFS. Meanwhile, Lerner became severely ill in 1986 and struggled for 10 years with CFS symptoms before treatment with antivirals dramatically improved his health.

Lerner, an infectious diseases specialist, runs his private CFS practice in Michigan, and his long-term tracking of patients' characteristics and response to treatment made this longitudinal research possible.

The fact that CFS patients experience different symptoms and multiple types of viral and bacterial infections has led researchers to believe CFS potentially has numerous causes. That lack of uniformity also complicates the diagnostic process and development of treatments.

"Part of the problem in trying to identify an agent or biomarkers for chronic fatigue syndrome is the extreme variability among people who say they have CFS. How to sort that out has held the field back a lot of years," said Glaser, who has studied the Epstein-Barr virus (EBV) for decades.

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