The protein “fingerprint” of the spinal fluids of people with Chronic Fatigue Syndrome (CFS) is distinct to that of people with Neurologic Post Treatment Lyme disease (nPTLS), and both fingerprints are also distinct to that of healthy people, according to a new study published in the journal PLoS ONE this week.

Patients with CFS and nPTLS report similar symptoms, so much so that many scientists regard CFS as an umbrella category that includes nPTLS. This study now questions that assumption.

The international team of researchers said their results also show that each condition has a multitude of candidate biomarkers that further studies that can validate to find the ones most likely to be effective in diagnostic tests.

The study is thought to be the most comprehensive analysis of the complete spinal fluid proteome (collection of proteins) to date for both CFS and nPTLS.

The findings also suggest that both conditions involve the central nervous system, and that their causes and effects are due to abnormalities in central nervous system proteins.

Led by Dr Steven E Schutzer, of the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, and Dr Richard D Smith, of Pacific Northwest National Laboratory, Richland, Washington, both in the US, the researchers analyzed the spinal fluid from three groups of people.

The people in the first group were 43 patients with CFS (they all met the 1994 International Chronic Fatigue Syndrome Study Group criteria); the second group was 25 patients diagnosed and treated for Lyme disease, but who had not completely recovered; and the third group was 11 healthy controls.

One of the reasons this study is unique is because the researchers used the latest methods of analyzing large groups of proteins so as to produce “fingerprints” of the proteome or collection of proteins that was unique to a group, and also unique to each person.

These latest methods use a protein separation technique called liquid chromatography coupled to mass spectrometry (LC-MS).

With these latest LC-MS techniques, the researchers detected 2,500 proteins in the “fingerprint” of each group: these included 738 proteins unique to the CFS group and 692 unique to the nPTLS group.

The researchers remarked that one of the interesting things about proteins that were common to both CFS and nPTLS, but in different amounts, was this could be a sign of both conditions being triggered by infection, but from different causes (all cases of nPTLS are triggered by the bacterium B. burgdorferi, whereas we don’t know yet which agents trigger most cases of CFS).

“This represents the type of data that can be useful in the formulation of pathogenetic hypotheses,” they wrote.

Schutzer told the press that studying the properties of spinal fluid was like “a liquid window into the brain”.

“One next step will be to find the best biomarkers that will give conclusive diagnostic results,” he explained.

“In addition, if a protein pathway is found to influence either disease, scientists could then develop treatments to target that particular pathway,” he added.

The team are already working on enhancing the techniques so they and other researchers can “dig even deeper and get more information on these and other neurologic diseases”, said Smith, who called the findings of this study “the tip of our research iceberg”.

“Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome.”
Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, et al.
PLoS ONE, 2011, 6(2): e17287; published online 23 Feb 2011.

Additional source: The University of Medicine and Dentistry of New Jersey (press release, 23 Feb 2011).

Written by: Catharine Paddock, PhD