Cerebrospinal fluid profiles can differentiate between Lyme disease, ME/CFS and healthy controls

Expert Review of Proteomics, April 2011:

Cerebrospinal fluid (CSF) proteomic analysis has revealed a CSF profile that can differentiate between neurologic post-treatment Lyme disease syndrome (nPTLS), chronic fatigue syndrome (CFS) and healthy controls. Recent studies utilizing new techniques for proteomic analysis have allowed insight into the pathogenesis of these two mysterious conditions and may lead to improvements in their diagnosis and treatment in the future.

Chronic fatigue syndrome and nPTLS are two conditions in which patients often report common symptoms, including fatigue and cognitive dysfunction. Owing to their shared symptomology, methods to diagnose the two syndromes are needed. Both conditions have an unexplained pathology, and new insights into pathogenesis and potential treatments are needed.

The recent study, published in PLoS One, used new techniques in their analysis, which the authors noted were enabled by “advances in sample preparation, separations and MS platform capabilities”, to try and reveal more about which proteins were unique to each condition.

The team from the New Jersey Medical School (NY, USA) analyzed CSF from 43 patients who fulfilled the clinical criteria for CFS, 25 patients who had been treated for confirmed Lyme disease but did not completely recover (nPTLS) and 11 healthy control subjects.

The samples were first subjected to whole proteome analyses of the CSF using liquid chromatography coupled to mass spectrometry. In order to do this, immunoaffinity depletion of the 14 most abundant proteins and strong cation exchange fractionation was enacted to prevent protein masking and reduce sample complexity of the proteome. This method yielded over 2500 detectable proteins for each group.

Individual patient analysis employing a mass spectrometry-based label-free quantitative analysis approach found that CFS and nPTLS patients could be separated from each other and from the healthy controls by their specific CSF protein profile (p < 0.01).

Therefore, it is thought that these methods could be used as diagnostic tools for both of the conditions in the future. Moreover, these results, the most comprehensive analysis of the CFS and nPTLS proteome, could also reveal more about the pathogenic processes of both conditions and lead to potential new treatments.

“One next step will be to find the best biomarkers that will give conclusive diagnostic results,” commented first author Steven Schutzer of the University of Medicine and Dentistry of New Jersey, (NY, USA). “In addition, if a protein pathway is found to influence either disease, scientists could then develop treatments to target that particular pathway.”

On a broader scale, the team also hopes that their proteomic strategy will accelerate the discovery of candidate biomarkers for other clinical applications in the future. By using quantitative analysis that did not require previous knowledge of specific CSF proteins, they hope that their method will accelerate the transition from the discovery phase to validation of CSF biomarkers in a variety of conditions.

Sources: Schutzer SE, Angel TE, Liu T et al. Distinct cerebrospinal fluid proteomes differentiate post-treatment Lyme disease from chronic fatigue syndrome. PLoS One 6(2), e17287 (2011); University of Medicine and Dentistry of New Jersey newsroom: www.umdnj.edu