Spinal Fluid Proteins Distinguish Lyme Disease from Chronic Fatigue Syndrome ++

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Date: 02-23-11

Name: Jerry Carey or Rob Forman

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Spinal Fluid Proteins Distinguish Lyme Disease from Chronic Fatigue Syndrome http://bit.ly/gggdiP

NEWARK, NJ - Patients who suffer from Neurologic Post Treatment Lyme disease (nPTLS) and those with the Chronic Fatigue Syndrome report similar symptoms.

However unique proteins discovered in spinal fluid can distinguish those two groups from one another and also from people in normal health, according to new research conducted by a team led by E. Schutzer, MD, of the University of Medicine and Dentistry of New Jersey – New Jersey Medical School, and D. , Ph.D., of Pacific Northwest National Laboratory.

This finding, published in the journal PLoS ONE (February 23, 2011), also suggests that both conditions involve the central nervous system and that protein abnormalities in the central nervous system are causes and/or effects of both conditions.

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The investigators analyzed spinal fluid from three groups of people.

One group consisted of 43 patients who fulfilled the clinical criteria for Chronic Fatigue Syndrome (CFS).

The second group consisted of 25 patients who had been diagnosed with, and treated for, Lyme disease but did not completely recover.

The third group consisted of 11 healthy control subjects.

*Spinal fluid is like a liquid window to the brain,*

says Dr. Schutzer. By studying the spinal fluid, the research team hoped to find abnormalities that could be used as markers of each condition and could lead to improvements in diagnosis and treatment.

Taking advantage of previously unavailable methods for detailed analysis of spinal fluid, the investigators analyzed the fluid by means of high powered mass spectrometry and special protein separation techniques.

They found that each group had more than 2,500 detectable proteins. The research team discovered that there were

1) 738 proteins that were identified only in CFS but not in either healthy normal controls or patients with nPTLS;

2) 692 proteins found only in the nPTLS patients.

Previously there had been no available candidate biomarkers to distinguish between the two syndromes, nor even strong evidence that the central nervous system is involved in those conditions.

This research represents the most comprehensive analysis of the complete spinal fluid proteome (collection of proteins) to date for both Chronic Fatigue Syndrome and Neurologic Post Treatment Lyme disease (nPTLS).

Prior to this study, many scientists believed that CFS was an umbrella category that included nPTLS. However these results call those previous suppositions into question

According to Dr. Schutzer, spinal fluid proteins can likely be used as a marker of disease, and this study provides a starting point for research in that area.

*One next step will be to find the best biomarkers that will give conclusive diagnostic results,*

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

*Newer techniques that are being developed by the team will allow researchers to dig even deeper and get more information for these and other neurologic diseases*,

says Dr. .

*These exciting findings are the tip of our research iceberg*

Other authors included E. Angel, Tao Liu, Athena A. Schepmoes, Therese R. Clauss, N. Adkins and G. Camp II of PNNL; Bart K. Holland of UMDNJ-New Jersey Medical School; Jonas Bergquist of Uppsala University in Sweden; P.K. Coyle of SUNY-Stony Brook; A. Fallon of Columbia University; H. Natelson of UMDNJ, Beth Israel Medical Center and Albert Einstein School of Medicine.

Funding sources included the National Institutes of Health, through NIAID, NIDA, NINDS, the National Center for Research Resources, the Swedish Research Council, Uppsala Berzelii Technology Center for Neurodiagnostics, SciLifeLab-Uppsala, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory. Time for Lyme, Lyme Disease Association, and the Tami Fund.

Journal citation: Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, et al. (2011) Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome. PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287

The article is available at the PLoS ONE website (see below)

About UMDNJ:

The University of Medicine and Dentistry of New Jersey (UMDNJ) is the nation's largest free-standing public health sciences university with more than 6,000 students attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and its only school of public health on five campuses. Annually, there are more than two million patient visits at UMDNJ facilities and faculty practices at campuses in Newark, New Brunswick/Piscataway, Scotch Plains, Camden and Stratford. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, which provides a continuum of healthcare services with multiple locations throughout the state.

About Pacific Northwest National Laboratory:

Pacific Northwest National Laboratory is a Department of Energy Office of Science national laboratory where interdisciplinary teams advance science and technology and deliver solutions to America's most intractable problems in energy, the environment and national security. PNNL employs 4,900 staff, has an annual budget of nearly $1.1 billion, and has been managed by Ohio-based Battelle since the lab's inception in 1965. Follow PNNL on Facebook, LinkedIn and Twitter.

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Research Article

Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome

http://bit.ly/hKVZxW

E. Schutzer1#*, E. Angel4#, Tao Liu4#, Athena A. Schepmoes4, Therese R. Clauss4, N. Adkins4, G. Camp II4, Bart K. Holland3, Jonas Bergquist5, K. Coyle6, D. 4, A. Fallon7, H. Natelson2,8

1 Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America, 2 Department of Neurology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America, 3 Division of Biostatistics and Epidemiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America, 4 Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America, 5 Department of Physical and Analytical Chemistry, Uppsala University, Uppsala, Sweden, 6 Department of Neurology, State University of New York-Stony Brook, Stony Brook, New York, United States of America, 7 Department of Psychiatry, Columbia University Medical Center, New York, New York, United States of America, 8 Department of Pain Medicine and Palliative Care and Beth Israel Medical Center, Albert Einstein School of Medicine, Bronx, New York, United States of America

Abstract

Background

Neurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology.

They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.

Methods and Principal Findings

Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry (MS), coupled with immunoaffinity depletion methods to reduce protein-masking by abundant proteins.

Individual patient and healthy control CSF samples were analyzed directly employing a MS-based label-free quantitative proteomics approach.

We found that both groups, and individuals within the groups, could be distinguished from each other and normals based on their specific CSF proteins (p<0.01).

CFS (n = 43) had 2,783 non-redundant proteins, nPTLS (n = 25) contained 2,768 proteins, and healthy normals had 2,630 proteins.

Preliminary pathway analysis demonstrated that the data could be useful for hypothesis generation on the pathogenetic mechanisms underlying these two related syndromes.

Conclusions

nPTLS and CFS have distinguishing CSF protein complements. Each condition has a number of CSF proteins that can be useful in providing candidates for future validation studies and insights on the respective mechanisms of pathogenesis. Distinguishing nPTLS and CFS permits more focused study of each condition, and can lead to novel diagnostics and therapeutic interventions.

The full text can be found:

In HTML at: http://bit.ly/hKVZxW

In PDF format: http://bit.ly/g2qGI6