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

Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America.
PLoS ONE (Impact Factor: 3.23). 02/2011; 6(2):e17287. DOI: 10.1371/journal.pone.0017287
Source: PubMed


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.
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.
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.

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Available from: Tao Liu, Oct 02, 2015
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    • "The question whether the label ME is appropriate (Baraniuk et al., 2005; Schutzer et al., 2011) or not remains to be established, but considering the confusion due to the introduction of chronic fatigue as the principle criterion and the use of symptom-based criteria and questionnaires in clinical practice and research, it seems crucial to assess various characteristic symptoms objectively and to make a clear distinction between patients with postexertional malaise (ME) and patients without post-exertional malaise. Objective tests, e.g., repeated exercise tests (CPETs) and tilt table testing, could be employed as a solid basis for the diagnosis , the validation, adjustment and refinement of ME (Carruthers et al., 2011) and CFS (Fukuda et al., 1994) criteria and the definition of clinical ME and CFS patients subgroups in research. "
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    ABSTRACT: Myalgic Encephalomyelitis (ME) was identified as a new clinical entity in 1959 and has been acknowledged as a disease of the central nervous system/neurological disease by the World Health Organisation since 1969. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after minor exertion, are distinctive symptoms of ME.Chronic Fatigue Syndrome (CFS) was introduced in 1988 and was redefined into clinically evaluated, unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of a list of eight symptoms, e.g. headaches and unrefreshing sleep, in 1994.Although the labels are used interchangeably, ME and CFS define distinct diagnostic entities. Post-exertional malaise and cognitive deficits e.g. are not mandatory for the diagnosis CFS, while obligatory for the diagnosis ME. “Fatigue” is not obligatory for the diagnosis ME.Since fatigue and other symptoms are subjective and ambiguous, research has been hampered. Despite this and other methodological issues, research has observed specific abnormalities in ME/CFS repetitively, e.g. immunological abnormalities, oxidative and nitrosative
    Frontiers in Physiology 03/2014; 5:109. DOI:10.3389/fphys.2014.00109 · 3.53 Impact Factor
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    • "By this way, our study on a couple of twins could permit the focusing on some biomarkers representing the prelude to a targeted search for these proteins in a wide number of patients, in order to confirm their usefulness in the diagnosis and therapy of CFS. At present, few proteomics works on CFS have been carried out on cerebrospinal fluid [32,33], and on serum [34] while in our study we decided to explore the WS of CFS patient preferring to adopt a less invasive procedure in collecting the samples. Although WS is a less complex fluid, it has been proved to be a promising diagnostic tool [23-28], and we found an alteration of protein patterns in the patient in respect to his control. "
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    ABSTRACT: Chronic Fatigue Syndrome (CFS) is a severe, systemic illness characterized by persistent, debilitating and medically unexplained fatigue. The etiology and pathophysiology of CFS remains obscure, and diagnosis is formulated through the patient's history and exclusion of other medical causes. Thereby, the availability of biomarkers for CFS could be useful for clinical research. In the present study, we used a proteomic approach to evaluate the global changes in the salivary profile in a couple of monozygotic twins who were discordant for CFS. The aim was to evaluate differences of salivary protein expression in the CFS patient in respect to his healthy twin. Saliva samples were submitted to two-dimensional electrophoresis (2DE). The gels were stained with Sypro, and a comparison between CFS subject and the healthy one was performed by the software Progenesis Same Spot including the Analysis of variance (ANOVA test). The proteins spot found with a >=2-fold spot quantity change and p<0.05 were identified by Nano-liquid chromatography electrospray ionization tandem mass spectrometry. To validate the expression changes found with 2DE of 5 proteins (14-3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc-alpha-2-glycoprotein), we used the western blot analysis. Moreover, proteins differentially expressed were functionally analyzed using the Ingenuity Pathways Analysis software with the aim to determine the predominant canonical pathways and the interaction network involved. The analysis of the protein profiles allowed us to find 13 proteins with a different expression in CFS in respect to control. Nine spots were up-regulated in CFS and 4 down-regulated. These proteins belong to different functional classes, such as inflammatory response, immune system and metabolism. In particular, as shown by the pathway analysis, the network built with our proteins highlights the involvement of inflammatory response in CFS pathogenesis. This study shows the presence of differentially expressed proteins in the saliva of the couple of monozygotic twins discordant for CFS, probably related to the disease. Consequently, we believe the proteomic approach could be useful both to define a panel of potential diagnostic biomarkers and to shed new light on the comprehension of the pathogenetic pathways of CFS.
    Journal of Translational Medicine 10/2013; 11(1):243. DOI:10.1186/1479-5876-11-243 · 3.93 Impact Factor
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    • "Mass spectrometry (this term is spelled out or if preceded by LC or if referring to tandem mass spectrometry it appears as MS, italicized this to distinguish it from the disease multiple sclerosis which is abbreviated as MS non-italicized) based proteomics offers an effective tool to evaluate CSF proteins. Using advanced proteomic techniques, we have previously examined CSF collected from healthy controls [8], and two disease groups with confounding symptoms, chronic fatigue syndrome (CFS) and neurologic post treatment Lyme disease syndrome (nPTLS) [9]. The proteomic results permitted separation of one disease from another. "
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    ABSTRACT: The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.
    PLoS ONE 09/2013; 8(9):e66117. DOI:10.1371/journal.pone.0066117 · 3.23 Impact Factor
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