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BREAKTHROUGH: New Spinal Fluid Analysis Distinguishes Lyme from CFS

eric_s

Senior Member
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Location
Switzerland/Spain (Valencia)
http://www.prohealth.com/library/showarticle.cfm?libid=15959

February 23, 2011


New tests suggest the central nervous system is involved in ME/CFS and Lyme, and that protein abnormalities in the CNS are causes and/or effects of both conditions. [Note: this news will be highlighted tonight - Feb 23 - on "The CBS Evening News with Katie Couric." The episode will be offered at Evening News online http://www.cbs.com/cbs_evening_news]

Patients who suffer from Neurologic Post Treatment Lyme disease (nPTLS) and those with 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, at the University of Medicine and Dentistry of New Jersey and Richard D. Smith, PhD, at Pacific Northwest National Laboratory.

Their findings, published Feb 23 by the free access journal PLoS ONE ( Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome), also suggest:

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:

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

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.

Source: University of Medicine and Dentistry of New Jersey, press release, Feb 23, 2011
 

urbantravels

disjecta membra
Messages
1,333
Location
Los Angeles, CA
Here's the press release from the University (no dentists involved in this research; it's just part of the name of the university)

http://www.umdnj.edu/cgi-bin/cgiwra...sh+Lyme+Disease+from+Chronic+Fatigue+Syndrome

A report from the New Jersey Star-Ledger:

http://www.nj.com/news/index.ssf/2011/02/umdnj_report_identifies_protei.html

Amy Dockser Marcus at wsj.com:

http://blogs.wsj.com/health/2011/02...drome-and-lyme-disease/?mod=google_news_blog#

See my comment, the first, in response to Suzanne Vernon: POKE MY SPINE, PLEASE!!!
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Here's the paper:

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017287

Steven E. Schutzer1#*, Thomas E. Angel4#, Tao Liu4#, Athena A. Schepmoes4, Therese R. Clauss4, Joshua N. Adkins4, David G. Camp II4, Bart K. Holland3, Jonas Bergquist5, Patricia K. Coyle6, Richard D. Smith4, Brian A. Fallon7, Benjamin 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.



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

Editor: Howard Gendelman, University of Nebraska, United States of America


Received: November 29, 2010; Accepted: January 26, 2011; Published: February 23, 2011

Copyright: 2011 Schutzer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: National Institutes of Health, through NIAID (grant AI088765), NIDA (grant DA021071), NINDS (grant NS38636), the National Center for Research Resources (RR018522), the Swedish Research Council (621-2008-3592), Uppsala Berzelii Technology Center for Neurodiagnostics, SciLifeLab-Uppsala, Time for Lyme, Lyme Disease Association, and the Tami Fund for support of portions of the research. Pacific Northwest National Laboratory units are located in the Environmental Molecular Sciences Laboratory, a national scientific user facility, sponsored by the Department of Energy (DOE), operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RL0 1830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: schutzer@umdnj.edu

# These authors contributed equally to this work.
 

George

waitin' fer rabbits
Messages
853
Location
South Texas
Hey if a headache inducing, pain creating, muscle cramping spinal tap will get me a correct diagnosis and even the hint of possible treatments. . . . Where do I sign up??? (grins) I don't know about Dr. Vernon but I'm so sick that a spinal tap is no worse than grocery shopping for me so I'd sign up in a heart beat. (just give me a nice bone to bite when they stick the needle in!)

Now here's a silly question. . . so where did all those unique proteins come from? anyone, anyone, Buller? I mean could viruses cause all those proteins? Or maybe a retrovirus that produces proteins? Or oh, no don't tell me it's the fact that I'm wearing my false illness belief corset,(Well UT said she didn't want it any more, grins) that caused all those weird proteins?
 

CBS

Senior Member
Messages
1,522
Now here's a silly question. . . so where did all those unique proteins come from? anyone, anyone, Buller? I mean could viruses cause all those proteins? Or maybe a retrovirus that produces proteins? Or oh, no don't tell me it's the fact that I'm wearing my false illness belief corset,(Well UT said she didn't want it any more, grins) that caused all those weird proteins?

And while I longer look good in it, I've so desperately clung to mine as emotionally, I need it (the self delusional notion that it was flattering) more than I need to rejoin society as that would require I confront my fears and initiate the hard work of searching my sole in order to regain my health. Yet, if I were to resume my role as a contributing member of society I may no longer need the constraint I find impossible to resist.

Please someone get me Peter White's phone number before this epiphany fades! :victory:
 

George

waitin' fer rabbits
Messages
853
Location
South Texas
And while I longer look good in it, I've so desperately clung to mine as emotionally, I need it (the self delusional notion that it was flattering) more than I need to rejoin society as that would require I confront my fears and initiate the hard work of searching my sole in order to regain my health. Yet, if I were to resume my role as a contributing member of society I may no longer need the constraint I find impossible to resist.

Please someone get me Peter White's phone number before this epiphany fades! :victory:

(SNORT!) And your corset goes so well with your biker bandana and leather coat. Most people don't know that your little kid pic is sitting on a harley. (grins) I have to say the pink lace's are a great contrast with the black leather. Man you could start a trend amoung the Wessly, White and Chalder gang. (Snort!)
 

urbantravels

disjecta membra
Messages
1,333
Location
Los Angeles, CA
OK, I'm just going to try to clear the image of CBS in a corset from my mind long enough to focus my mind on the actual question, and quote once again from the CAA report on the paper:

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 disease groups. The complement system is a part of the immune system that helps to clear infectious pathogens. Interestingly, in a 2005 proteomics study conducted by James N. Baraniuk and published in BMC Neurology, the complement system proteins were also found in cerebrospinal fluid from CFS patients and differentiated CFS patients from healthy controls. Alterations in the complement cascade pathways have been a relatively consistent abnormality in CFS patients (Sorensen B, et al., 2003 and 2009). This convergence of data implicates biomarkers and pathways that should be prioritized for verification and validation.

my emphasis...

Googling "complement cascade" quickly got me in over my head, but it appears to be a chain reaction of different immune system proteins that goes along several different pathways to try and kill pathogens. There are cytokines in there, by the way..

My only-slightly-educated guess is that having these proteins elevated could possibly either mean the body is trying to fight a chronic infection(s), or it could mean the immune system is activated for some other reason. Neither of which would be surprising new hypotheses about the cause of ME/CFS.

I can't help wondering which of these proteins might match up with elevated cytokines per the Lights' research.
 

Enid

Senior Member
Messages
3,309
Location
UK
Like a "hole in one" to me eric. Never doubted ME should have been investigated more at "spinal tap" stage - mine showing abnormalities there and in the brain which were never pursued.
 

SilverbladeTE

Senior Member
Messages
3,043
Location
Somewhere near Glasgow, Scotland
Hey Wessely, Sharpe etc, EAT CROW!!! :p

and no that's not some bizzare threat, anyone but a retard would know that's reffering to being "made ot eat humble pie" after being arrogant and rotten to people. Smiley, this thing ":p" indicates humour/sarcasm and/or satire.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
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 disease groups. The complement system is a part of the immune system that helps to clear infectious pathogens. Interestingly, in a 2005 proteomics study conducted by James N. Baraniuk and published in BMC Neurology, the complement system proteins were also found in cerebrospinal fluid from CFS patients and differentiated CFS patients from healthy controls. Alterations in the complement cascade pathways have been a relatively consistent abnormality in CFS patients (Sorensen B, et al., 2003 and 2009). This convergence of data implicates biomarkers and pathways that should be prioritized for verification and validation.
I didn't know this! And this was not investigated instantaneously, research projects funded, doctors educated?!?! What the hell is wrong with the people in those positions? I have not read the Baraniuk and Sorensen papers yet, but how could anyone still doubt ME/CFS is real and physical after those, if they found a statistically significant difference?

Edit: Those studies were published in 2003, 2005 and 2009 and i have not heard one doctor tell me about it!!! Seriously! Are they actually good for anything (the doctors)?
 

Enid

Senior Member
Messages
3,309
Location
UK
Quite eric - 10 years ago left a major UK Neurology Unit (well speechless and had to be escorted/driven everywhere) after my lumbar puncture showing brain "high spots" and spinal column abnormalties. Rapid decline followed (all ME problems) from which never fully recovered. My own guess "high spots" something to do with "tangling" due to the presence of abnormal proteins. For nothing was diagnosed.
 
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