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Journal of IiME Volume 6 Issue 1 (June 2012) various antibodies, and the presence of immune complexes. These changes support the conclusion that dysregulation of cellular and humoral response are associated with CFS…..The pattern of immune abnormalities suggests that immunologic factors may contribute to the pathogenesis….It seems plausible that the overproduction of some cytokines contributes to the fatigue. The recent demonstration of activation of the 2-5A synthetase pathway (associated with interferon- signal transduction) in some (ME)CFS patients provides support for this hypothesis…The search for infectious agents in (ME)CFS patients should be initially guided by…the detection of circulating antibodies and antigens to agents that have been implicated in (ME)CFS….A good experimental model…should…utilise wellcharacterised and homogeneous subject populations…. The panel recommends the implementation of longitudinal studies that include the following key elements: wellcharacterised cases and controls; assays designed to measure immune function: (a) natural killer cell activity; (b) percentage of peripheral blood lymphocytes expressing activation markers; (c) pro-inflammatory cytokines and soluble receptors; (d) Th-1 and Th-2 responses; (e) activity of the 2-5A synthetase pathway, and (f) serum immunoglobulin levels; selected measures of autonomic nervous system and neuroendocrine functioning; functional magnetic resonance imaging studies; studies… to demonstrate the presence or absence of viral/microbial genetic material….The use of interdisciplinary, multi-site (including international) longitudinal studies to explore links between the variations noted in (ME)CFS patients’ immune, neuroendocrine, and cardiovascular systems is critical to developing an understanding of relationships among causal factors, symptom progression, and recovery…. Three primary methodological barriers impair the investigations of (ME)CFS: poor study design, the heterogeneity of the CFS population, and the lack of standardised laboratory procedures. The quality of previous CFS research (is hampered by) multiple differences in methods of subject recruitment and classification (and) clinical definitions applied and outcome measures used. It is our obligation to overcome the methodological barriers outlined above” (Gerrity TR et al. NeuroImmunoModulation 2004:11(6):351-357). Invest in ME (Charity Nr. 1114035) 2004 “Patients (with ME/CFS) are more likely to have objective abnormalities of the immune system than control subjects. We measured the frequency of certain HLA antigens (and) restricted our analysis to Class II molecules, as these appear to be more specific predictors of susceptibility to immunologically-based disorders. The frequency of the HLA-DQ1 antigen was increased in patients compared to controls. This association between (ME)CFS and the HLA-DQ1 antigen translates into a relative risk of 3.2” (RS Schacterle, Anthony L Komaroff et al. JCFS 2004:11(4):33-42). 2004 The Seventh Biennial AACFS International Research and Clinical Conference was held on 8th – 10th October 2004 at Maddison, Wisconsin. It was attended by 120 doctors and 112 patients, and research presenters came from people from about 16 different countries, but Professor Klimas commented that there was no-one from England (in discussion afterwards, she said “But none from England this year, and I don’t know why”). As one attendee put it: “Her statement was one of dismayed puzzlement…it was spoken by a busy researcher who doesn’t have time for politics and is completely baffled why (researchers from the UK) are no longer present at the research symposium…. Probably the most expressive part of Dr Klimas’ comment was her non-verbal expression – she was expressing deep and personal concern” (private communication). As another person observed: “I was assured by the Department of Health that those running the PACE Trial are international specialists, yet not one of them thought it necessary to attend such an important international conference where the ‘immunologic and neurologic malfunctions’ of ME/CFS featured so strongly. Doesn’t that just say it all?” (private communication). Professor Anthony Komaroff (Harvard) began the conference with an over-view of current research, saying that research has shown abnormalities in many systems: “Studies of immune activation indicate that activated lymphocytes can pass through the blood-brain barrier in small www.investinme.org Page 69 of 108

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