Journal of IiME Volume 6 Issue 1 (June 2012) was sponsored by The CFIDS Association, the US Centres for Disease Control, and the National Institutes of Health Office of Research on Women’s Health and was the third in a series of scientific symposia on (ME)CFS. This series of (ME)CFS assessment symposia series was designed to examine the role of the neurological, endocrine, circulatory and immune systems in (ME)CFS. The Immune System symposium developed a strategy on key issues surrounding the immune system in (ME)CFS, with agreement on the following: (i) The immune system is involved in (ME)CFS: substantial published evidence shows that many (ME)CFS patients have immunological abnormalities; (ii) infections may also play a role: the panel concluded that direct and indirect evidence points to the involvement of active viral or bacterial infections in some case of (ME)CFS; (iii) (ME)CFS is a multi-system disorder: in addition to the immune system, the endocrine and autonomic nervous systems may be implicated and (iv) more research is needed to define the immunological aspects of (ME)CFS. The symposium particularly noted “the inappropriate practice of combining patients with…various comorbid conditions in studies and then attempting to draw conclusions across the subgroups” (The CFIDS Chronicle, Winter (January) 2002; The CFS Research Review, Winter (January) 2002:3:1). 2001 In December 2001 The Alison Hunter Memorial Foundation (AHMF) hosted the third international ME/CFS Research and Clinical Scientific Meeting in Sydney, Australia; the AHMF is an enduring memorial to Alison Hunter and to all those whose lives have been devastated by ME/CFS. Alison died aged 19 in 1996 from severe ME, suffering seizures, paralysis, gastrointestinal paresis, severe recurrent mouth ulcers and overwhelming infection, having courageously fought ME/CFS for ten years. Professor Anthony Komaroff (Harvard) spoke on “The Biology of ME/CFS”, noting that immune abnormalities are seen more often in patients, including low levels of circulating immune complexes, elevated total complement (CH50), elevated IgG, atypical lymphocytosis and low levels of antinuclear antibodies (ANA). Invest in ME (Charity Nr. 1114035) Immunological studies have revealed a variety of immunological abnormalities, especially impaired function of natural killer cells and increased numbers of activated CD+T cells. Whilst neither finding is specific enough to constitute a diagnostic marker, they are nevertheless consistent with a chronically activated immune system in ME/CFS. Two groups have reported what appears to be a more specific immune system abnormality in ME/CFS: an increased activity of the 2-5A enzymatic pathway in lymphocytes. Patients with ME/CFS were very different from those with depression, fibromyalgia and healthy controls. The evidence indicates an organic basis, with abnormal regulation of the immune system. Dr Patrick Englebienne and Professor Kenny De Meirleir (Brussels) spoke on “CFS and MS as Subsets of a Group of Cellular Immune Disorders”. Apoptosis (programmed cell death) is a critical component of adaptive cellular immunity. When challenged by infection, type I interferons elicit apoptotic responses by inducing the expression of 2-5A synthetase (2-5OAS), RNaseL and the p68 dependent kinase (PKR). Results from the authors’ laboratories point to an improper activation of 25OAS in monocytes of both patients with ME/CFS and with chronic (but not in relapsing/remitting) MS, which results in an inappropriate activation of RNaseL. This process ultimately leads to a blockade of the RNaseL-mediated apoptotic programme and it supports the involvement of environmental factors. Such cellular stress is capable of generating small RNA fragments and/or of inducing the transcription of endogenous retrovirus sequences. The ‘abnormal’ RNA sequences are responsible for the inappropriate activation of 2-5OAS and have been implicated in the aetiology of both ME/CFS and MS. Depending on their origin and structure, these RNA fragments are capable of either activating or down-regulating PKR. This results in a differential effect not only on the PKR/RNaseL-mediated apoptotic programmes but also on the activation by PKR of the inducible NO (nitric oxide) synthetase. A release of nitric oxide at either high rates (as in ME/CFS) or low rates (as in chronic MS) by lymphocytes has corollary consequences, triggering the skeletal and cardiac muscle ryanodine receptors (calcium channels), NK cell function, COX2 activation and glutamate release by activated T-cells in the brain. Glutamate www.investinme.org Page 62 of 108
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