Journal of IiME Volume 6 Issue 1 (June 2012) dysfunction are common manifestations of (ME)CFS…Because several immune abnormalities have been associated with this syndrome, the disorder has also been termed chronic fatigue immune dysfunction syndrome…A characteristic of (ME)CFS is a disordered immune system characterised by abnormal cell-surface marker expression and cellular immune function. …In patients manifesting incapacitating symptoms, the CD8+11b+ population is considerably reduced, and this reaches statistical significance….in agreement with the findings of other investigators, a decrease in NK cell-mediated lysis appears to be directly related to symptoms observed in (ME)CFS…The loss of these regulatory cells may allow for enhanced activation of other CD8+ lymphocytes such as the cytotoxic cells. Activated cells can over-produce cytokines that cause the symptoms characteristic of (ME)CFS” (Edward Barker, Alan L Landay, Jay A Levy et al. Clin Inf Dis 1994:18: (Suppl 1): S136-41). 1994 “Overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested…In patients with (ME)CFS – but not in controls – serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analysed) with relative amounts (as compared to betaglobin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral blood mononuclear cells….These findings point to polycellular activation…. The immune system is a readily accessible, sensitive indicator of environmental or internal changes, and studies conducted by different groups over the past few years have provided valuable evidence for changes in immune status among individuals with (ME)CFS…. To gain insight into the nosology and aetiology of (ME)CFS, we assessed patterns of soluble immune mediator expression at the protein and mRNA levels in individuals with (ME)CFS….The data presented in this report are consistent with previous evidence of immune dysregulation among patients with (ME)CFS and point to a dysregulation of TNF (tumour necrosis factor) expression as a distinctive feature of this condition….Imbalances in TNF and associated changes in levels of other cytokines may underlie Invest in ME (Charity Nr. 1114035) many of the characteristic features of (ME)CFS…. In addition, TNF- can have deleterious effects on the central nervous system” (Roberto Patarca, Nancy G Klimas et al. Clin Inf Dis 1994:18: (Suppl 1):S147-153). Tumour necrosis factor is a cytokine involved in systemic inflammation. Its primary role is in the regulation of immune cells. Increased TNF causes apoptosis, inflammation and tumorigenesis. 1994 “The chronic fatigue immune dysfunction syndrome (CFIDS) is a major subgroup of the chronic fatigue syndrome (CFS)…. We and other investigators have reported a strong association between immune dysfunction and a serological viral activation pattern among patients in this group. This finding appeared similar to that for a variety of conditions, such as chronic active hepatitis…and systemic lupus erythematosus, in which a definite association between a particular HLA-DR/DQ haplotype and increased disease frequency has been reported. We thus elected to examine a cohort of patients with CFIDS, with use of HLA-DR/DQ typing…. A significant association between CFIDS and the presence of HLA-DQ3 was noted…. The association with HLA-DQ3 could represent an additive effect for patients who also have HLA-DR4 and/or HLA-DR5…. The results presented are intriguing. DQ3… was significantly more prevalent in patients than the …control groups. It is possible that DR4 and DR5 are also associated with an increased risk of developing CFIDS…. These findings strongly suggest that further evaluation of persons with CFIDS, including an investigation of an HLA Class I linkage dysequilibrium…are warranted….The data presented herein suggest that CFIDS, together with a variety of immune-mediated diseases…may share similar sequences of pathogenic mechanisms….It may be speculated that in a subpopulation (of CFIDS), a genetic predisposition may be triggered immunologically by any number of potential stimuli, resulting in a state of chronic immune dysequilibrium. This model could easily explain the recent findings with regard to acute viral infections, chronic active viral infection (and) allergies” (RH Keller, N Klimas, MA Fletcher et al. Clin Inf Dis 1994:18: (Suppl 1): S154-156). www.investinme.org Page 46 of 108
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