MAGICAL MEDICINE: HOW TO MAKE AN ILLNESS ... - Invest in ME

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identifying biomarkers…It is noteworthy that one gene, the CMRF35 antigen precursor, was detected as differentially
expressed by all analytical approaches. This gene encodes a cell membrane antigen that is a member of the
immunoglobulin superfamily (and) is thought to control interactions between T cells and antigen presenting cells or
target (virus‐infected or mutated) cells that have to be killed…The CMRF35 antigen was highly expressed in the
CFS group…All of these genes implicate immune dysfunction in the pathophysiology of CFS” (Suzanne D
Vernon et al. Disease Markers 2002:193‐199).
2004
“We used differential‐display PCR of PMBCs to search for candidate biomarkers for CFS….86% of the differences were
present at baseline. Differential expression of ten genes was verified by real‐time reverse transcription PCR: five
(including perforin) were downregulated and the remaining five genes were upregulated…Many of these genes have
known functions in defence and immunity, thus supporting prior suggestions of immune dysregulation in the
pathogenesis of CFS…Differential‐display PCR is a powerful tool for identification of candidate biomarkers…Six of the
ten genes with verified differential expression have functions related to immune response. This adds strength to the
theory that dysregulation of immunity plays a major role in the biology of CFS” (Martin Steinau et al.
Journal of Molecular Medicine 2004: 10.1007/s00109‐004‐0586‐4).
2005
To test the hypothesis that there are reproducible abnormalities of gene expression in (ME)CFS patients
compared with healthy controls, Jonathan Kerr’s team analysed and compared gene expression in
peripheral blood mononuclear cells of ME/CFS patients with matched blood‐donor controls. Sixteen genes
were significantly different and were confirmed as having an expression profile associated with ME/CFS.
“These genes may be important in the pathogenesis of (ME)CFS and can be grouped according to immune, neuronal,
mitochondrial and other functions…These findings are consistent with previous work showing that patients with
(ME)CFS have evidence of immune activation, such as increased numbers of activated T cells and cytotoxic cells, and
raised circulating cytokine concentrations…NTE (neuropathy target esterase) is a target for organophosphates
and chemical warfare agents, both of which may precipitate (ME)CFS…. EIF2B4 is a mitochondrial translation
initiation factor and one of the EIFB2 family, within which mutations have been shown to be associated with central
nervous system hypomyelination and encephalopathy…. The involvement of genes from several disparate
pathways suggests a complex pathogenesis involving T cell activation and abnormalities of neuronal and
mitochondrial function, and suggests possible molecular bases for the recognised contributions of
organophosphate exposure and virus infection” (N Kaushik, ST Holgate, JR Kerr et al. J Clin Pathol
2005:58:826‐832).
(Neuropathy target esterase (NTE) is inhibited by several OP pesticides, chemical warfare agents, lubricants,
and plasticisers, leading to OP‐induced delayed neuropathy in humans, with over 30,000 cases of human
paralysis ‐‐ Gary Quistad et al. PNAS June 24, 2003:100:13:7983‐7987).
2006
“The single most influential gene was sestin 1 (SESN1), supporting recent evidence of oxidative stress involvement in
(ME)CFS…results suggest a common link between oxidative stress, immune system dysfunction and
potassium imbalance in (ME)CFS leading to impaired sympatho‐vagal balance strongly reflected in an
abnormal HRV (heart rate variability) (Gordon Broderick, Nancy Klimas et al. Pharmacogenomics
2006:7(3):407‐419).
2006
In a study of cytokine genomic polymorphisms in (ME)CFS, Italian researchers found “a highly significant
increase in TNF‐857 and CT genotypes among patients with respect to controls and a significant decrease of IFN
gamma low producers among patients with respect to controls…We hypothesise that (ME)CFS patients can have