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Journal of IiME Volume 6 Issue 1 (June 2012) interesting new findings relating to neutrophil apoptosis (increased cell death involving a particular type of white blood cell) that was reported in the Journal of Clinical Pathology (2004:57:891-893). The BMJ goes on to conclude: ‘Evidence is emerging that people with chronic fatigue syndrome may have a detectable immunological abnormality’. They may be 15 years behind the rest of us in coming to this conclusion, but better late than never!” (Co-Cure MED, NOTICE, 20th August 2004). 2004 “The exacerbation of symptoms after exercise differentiates (ME)CFS from several other fatigueassociated disorders. Research data point to an abnormal response to exercise in patients with (ME)CFS compared to healthy sedentary controls, and to an increasing amount of evidence pointing to severe intracellular immune dysregulation in (ME)CFS patients. The dysregulation of the 2-5A synthetase/RNase L pathway may be related to a channelopathy, capable of initiating both intracellular hypomagnesaemia in skeletal muscles and transient hypoglycaemia. This might explain muscle weakness and the reduction of maximal oxygen uptake, as typically seen in (ME)CFS patients. The activation of the protein kinase R enzyme, a characteristic feature in at least a subset of (ME)CFS patients, might account for the observed excessive nitric oxide (NO) production in patients with (ME)CFS. Elevated NO is known to induce vasodilation, which may cause and enhance post-exercise hypotension” (J Nijs, K De Meirleir, N McGregor, P Englebienne et al. Med Hypotheses 2004:62(5):759-765). 2004 “Immunological aberration (in ME/CFS) may be associated with an expanding group of neuropeptides and inappropriate immunological memory. Vasoactive neuropeptides act as hormones, neurotransmitters, immune modulators and neurotrophes. They are immunogenic and known to be associated with a range of autoimmune conditions. They are widely distributed in the body, particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, Invest in ME (Charity Nr. 1114035) blood cells and other tissues. They have a vital role in maintaining vascular flow in organs and are potent immune regulators with primary antiinflammatory activity. They have a significant role in protection of the nervous system (from) toxic assault. This paper provides a biologically plausible mechanism for the development of (ME)CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection or significant physical exercise. Such an occurrence would have predictably serious consequences resulting from the compromised function of the key roles these substances perform” (Staines DR. Med Hypotheses 2004:62(5):646-652). 2004 The November 2004 issue of NeuroImmunoModulation contained the Report of the Research Symposium on ME/CFS convened by the CFIDS Association and co-sponsored by the CDC and the NIH. The report is entitled “Immunologic Aspects of Chronic Fatigue Syndrome” and is important because it sets out the necessary direction of future research. “(ME)CFS is a serious health concern …. studies have suggested an involvement of the immune system. A Symposium was organised in October 2001 to explore the….association between immune dysfunction and (ME)CFS, with special emphasis on the interactions between immune dysfunction and abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with (ME)CFS. This paper represents the consensus of the panel of experts who participated in this meeting….Data suggest that persons with (ME)CFS manifest changes in immune responses that fall outside normative ranges…(ME)CFS seems to be a multi-system disorder….There is substantial evidence that a large proportion of patients has some immunologic abnormalities, including decreased natural killer 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. The humoral immune system has also shown frequent abnormalities, including hypergammaglobulinemia, increased titres of www.investinme.org Page 68 of 108

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