A CFS Biomarker?
Benjamin Natelson (UMDNJ): CFS & Proteomics Study
(as of 03/01/05)
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A CFS Biomarker? Benjamin Natelson (UMDNJ): CFS & Proteomics Study (as of 03/01/05) |
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Current Research Interest/Projects
Dr. Natelson's Faculty Bio & AACFS Experience
This faculty page includes a representation of his published studies along with contact information. Dr. Natelson is a well-known researcher in the field of both CFS and Gulf War illness and led a government clinic for 12 (?) years. He is also a past president of AACFS, has authored or coauthored more than 220 paper as well as 2 books—the most recent of which was published by Yale University Press and focuses on the common patient complaint of fatigue. Read about his many accomplishments at The AACFS website.
Current Research Interest/Projects
Dr. Natelson describes here not only one of his two major interests are but also tells the student why they should get involved in it. He says that he's interested in, "learning the cause of a newly recognized illness called the chronic fatigue syndrome or CFS. Patients with CFS have a chronic viral-like illness which is thought to influence brain function. We have begun a set of physiological, neuropsychological, and viral/immunological studies to characterize CFS and understand its cause. Getting involved in CFS research would provide a student with knowledge and skills that integrate neurosciences with other basic sciences as well as with clinical medicine." An abstract on Dr. Natelson's research project follows:
Spinal fluid abnormalities in patients with chronic fatigue syndrome
AUTHORS: Natelson BH, Weaver SA, Tseng CL, Ottenweller JE
JOURNAL: Clinical and Diagnostic Laboratory Immunology 2005; 12(1): 52-5
ADDRESS: CFS Cooperative Research Center and Department of Neurosciences and Department of Preventive Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey
ABSTRACT: Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls. Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having co-morbid depression than those with normal fluid. In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls. The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process
Comment by MERGE: This paper provides interesting evidence for cytokine abnormalities within the cerebrospinal fluid of some, but not all, CFS patients. There is extensive evidence available in the literature of immunological abnormalities in patients with CFS usually represented as a decrease in NK cell activity, an increase in the percentage of T cells expressing activation markers, decreased lymphocyte stimulation by certain mitogens and soluble antigens, and increased production of certain pro-inflammatory cytokines such as transforming growth factor ß1 (Kennedy et al. 2004). These abnormalities are usually presented as significant differences between the CFS patients and age and gender matched control subjects but this hides the fact that not all of the patients are different from the controls — that’s the problem with statistics — and for this reason none of these measurements can be afforded the status of a "marker".
Natelson et al. carried out a lumbar puncture on 44 CFS patients and 13 healthy controls and investigated the cerebrospinal fluid for white blood cells, protein concentration and cytokines. They found that thirty percent of CFS patients had elevations in protein levels and/or in white blood cell count relative to laboratory norms; in contrast, NONE of the control subject had such elevations. Just as important, the team of researchers stratified their patients in terms of symptom presentation and showed that the sub-group of patients without evidence of current depression had the highest rate of abnormalities in their spinal fluid. This adds further weight to the developing hypothesis that CFS is heterogeneous and that clinical examination, MRI imaging and neuropsychological testing can be used to delineate sub-groups of patients and that research studies need to address this problem by using adequate numbers of patients that are well characterized in terms of gender, age, type of onset (e.g., sudden vs gradual, viral vs stress), duration of symptoms, other concurrent clinical conditions and geographic occurrence (cluster vs isolated cases) (Gerrity et al.).
Is it possible that the abnormalities expressed in this paper could explain some of the symptoms of ME/CFS? The answer is yes they can explain some ME/CFS aspects but there is a gap in our knowledge as to how alterations in cytokine levels lead to the severe symptoms that some ME/CFS patients experience. The finding of an immune dysfunction with the central nervous system of some patients is important but just as significant is the emergent view that the term "CFS" needs to be unpacked, urgently.
References: Kennedy G, Spence VA, Underwood C, Belch JJF. Increased neutrophil apoptosis in chronic fatigue syndrome. Journal of Clinical Pathology 2004; 57: 891-893.
Timothy R, Gerrity TR, Papanicolaou DA, Amsterdam JD. Immunologic aspects of chronic fatigue syndrome. Neuroimmunomodulation 2004;11:351-357.
PMID: 15642984 [PubMed - in process]
A CFS, patient, Cort Johnson, (phoenix-cfs.org/The%20SITE/mainmenu.htm) wrote the following as to why he is giving to Natelson's research. He gave me permission to circulate it. As I have said on lots of lists, people may have other research they prefer to support and that's fine with me—this is the one with the matching appeal so that's partly why I gave to this one and why I'm focusing on it at the moment. The ME/CFS and FMS community(s) just needs to raise as big a pot for biomedical research as possible and to do that, given that we can't depend on governments to fund the sort of research we want (and certainly it's unlikely they'd fund every project we like), we need as many people as possible either fundraising and/or giving something, even if it is only a little. Apologies for all the mails on this but the appeal will be over soon. Tom K.
" I finally got my $20 in. Wish I could have done more. I hope people know that proteomics not just ANY study. It is about finding unique abnormalities in CFS and discovering new avenues of research. It is a new technology and offers the potential to really blast our understanding of CFS wide open. Every controversial and poorly understood disease should be investigated by genomics and proteomics because they have the ability to scan enormous amounts of data and find distinct abnormalities that might take decades of research to find otherwise. We really need this research.
"There isn't alot of CFS spinal tap fluid out there; spinal fluid extraction can be painful and its difficult to get. I would hazard a guess that Natelson is one of two doctors with a good supply of CFS spinal fluid. Many people think the only way to link the immune and cognitive and other symptoms in CFS is through the brain but the brain is difficult to access. What is going on in the brain is one of the real untapped frontiers in CFS research. Natelson has that access but he can't make full use of it. There could be a breakthrough just sitting there untouched for a lack of some money.
"Natelson is a particularly good person to do this research because he is well respected by 'both sides' of the issue. If you've read his book you know is both very compassionate and very conservative. Very traditional in focus, he does not believe in alternate health treatments for CFS. On the other hand he believes there is a organic basis for CFS. In addition he has been well funded by the NIH in the past. In short, he's the perfect person to do this researh—if he finds something, he has a track record that no one can ignore and it will get some attention."
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