The Promise of the Proteome

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

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