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Proteins in spinal fluid

Friday 25 February 2011

University of Medicine & Dentistry of New JerseyThe University of Medicine & Dentistry of New Jersey has published the results of research involving unique proteins found in spinal fluid:

 

Spinal Fluid Proteins Distinguish Lyme Disease from Chronic Fatigue Syndrome

Press Release

Date: 02-23-11
Name: Jerry Carey or Rob Forman
Phone: 856-566-6171 or 973-972-7276
Email: careyge@umdnj.edu; formanra@umdnj.edu

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 Steven E. Schutzer, MD, of the University of Medicine and Dentistry of New Jersey – New Jersey Medical School, and Richard D. Smith, 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.

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. Smith. "These exciting findings are the tip of our research iceberg.”

Other authors included Thomas E. Angel, Tao Liu, Athena A. Schepmoes, Therese R. Clauss, Joshua N. Adkins and David 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; Brian A. Fallon of Columbia University; Benjamin 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

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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The above originally appeared here.

And the CFIDS Association of America offers an analysis:

The Promise of the Proteome

Analysis of the PLoS ONE study

proteome
Figure 1: Venn diagram illustrating distribution of proteins identified
in the three groups

In an article titled, "Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease and CFS," Steven Schutzer and colleagues from six institutions tested samples collected by lumbar puncture from 43 CFS subjects, 25 subjects with documented Lyme disease who did not recover after standard antibiotic treatment (referred to in this paper as "nPTLS") and 11 healthy controls.

Using mass spectroscopy and liquid chromatography, the team was able to generate a comprehensive list of 30,000 peptides in the cerebrospinal fluid (CSF) samples pooled from subjects in each disease group. Of these 30,000 peptides, 738 proteins were found only in CFS subjects. The nPTLS samples had 692 unique proteins and the normal controls had 724 unique proteins. Differences in the amounts of various proteins were detected between groups and CFS and nPTLS had more proteins in common than with the healthy controls.

Looking at the biological pathways implicated by the different proteins identified, the team found that proteins in the complement cascade were elevated in abundance in the pooled nPTLS and CFS samples compared to controls, but at different levels for the two disease groups. The complement system is a part of the immune system that helps to clear infectious pathogens. Proteins involved in the CDK5 signaling pathway were significantly enriched in the CFS samples. Alterations in the CDK5 signaling pathway have been linked to Parkinson's disease and Alzheimer's disease.

By analyzing individual CSF samples, they determined that nPTLS patients are distinct from CFS patients. The ability to distinguish CFS and nPTLS on the basis of these proteins has important diagnostic implications. It also suggests different treatment approaches may be warranted. Some have proposed that nPTLS represents a subset of CFS; however, the authors of this paper conclude that their data does not support that concept.

In the final discussion section, the authors state, "CSF proteome analysis may provide important and meaningful insights into the biological processes modulated as a function of disease and facilitate the identification of protein candidates for further investigation." They suggest that by uncovering these candidates in cerebrospinal fluid, a targeted search in blood for these proteins is now possible.

This team of researchers provided the comprehensive list of proteins they identified as part of the open access paper. This will enable these and other investigators to explore and interrogate the data further. The collaborative effort across six institutions and multiple funding partners, use of new technologies for discovery and willingness to openly share data to advance the field represent an inspiring 21st century research initiative worthy of high hopes.

Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, Adkins NJ, Camp DG, Holland BK, Bergquist J, Coyle PK, Smith RD, Fallon BA, Natelson BH. (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

Click here to read the unabridged version of "The Promise of the Proteome" 

 

The full analysis can also be downloaded as a PDF file:

PDF

The Promise of the Proteome: Analysis of the PLoS ONE paper (PDF, 597KB)

 


 

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