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Chronic fatigue syndrome (CFS) is characterized by immune dysfunctions including chronic immune activation, inflammation, and alteration of cytokine profiles. T helper 17 (Th17) cells belong to a recently identified subset of T helper cells, with crucial regulatory function in inflammatory and autoimmune processes. Th17 cells are implicated in allergic inflammation, intestinal diseases, central nervous system inflammation, disorders that may all contribute to the pathophysiology of CFS. IL-17F is one of the pro-inflammatory cytokines secreted by Th17 cells. We investigated the association between CFS and the frequency of rs763780, a C/T genetic polymorphism leading to His161Arg substitution in the IL-17F protein. The His161Arg variant (C allele) antagonizes the pro-inflammatory effects of the wild-type IL-17F. A significantly lower frequency of the C allele was observed in the CFS population, suggesting that the His161Arg variant may confer protection against the disease. These results suggest a role of Th17 cells in the pathogenesis of CFS.

Background: Patients with chronic fatigue syndrome (CFS) present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances., Methods: Forty-eight patients who fulfilled 1994 Centers for Disease Control and Prevention criteria for CFS underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2',5'-oligoadenylate trimer. Basic descriptive statistical parameters were calculated., Results: Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L., Conclusions: The main findings are 1) validation of sleep latency problems and other sleep disturbances as already suggested by several authors; 2) alpha-delta intrusion seems associated with anxiety; and 3) elevated RNase L did not correlate with alpha-delta sleep.

Patients with chronic fatigue syndrome (CFS) experience chronic musculoskeletal pain which is even more debilitating than fatigue. Scientific research data gathered around the world enables clinicians to understand, at least in part, chronic musculoskeletal pain in CFS patients. Generalized joint hypermobility and benign joint hypermobility syndrome appear to be highly prevalent among CFS sufferers, but they do not seem to be of any clinical importance. On the other hand, pain catastrophizing accounts for a substantial portion of musculoskeletal pain and is a predictor of exercise performance in CFS patients. The evidence concerning pain catastrophizing is supportive of the indirect evidence of a dysfunctional pain processing system in CFS patients with musculoskeletal pain. CFS sufferers respond to incremental exercise with a lengthened and accentuated oxidative stress response, explaining muscle pain, postexertional malaise, and the decrease in pain threshold following graded exercise in CFS patients. Applying the scientific evidence to the manual physiotherapy profession, pacing self-management techniques and pain neurophysiology education are indicated for the treatment of musculoskeletal pain in CFS patients. Studies examining the effectiveness of these strategies for CFS patients are warranted.

A dysregulation in the 2',5'-oligoadenylate (2-5A)-dependent RNase L antiviral pathway has been detected in peripheral blood mononuclear cells (PBMC) of chronic fatigue syndrome (CFS) patients, which is characterized by upregulated 2-5A synthetase and RNase L activities, as well as by the presence of a low molecular weight (LMW) 2-5A-binding protein of 37-kDa related to RNase L. This truncated protein has been shown to originate from proteolytic cleavage of the native 83-kDa RNase L by m-calpain and human leukocyte elastase (HLE). We investigated the possible role of 2-5A oligomers in the proteolytic action toward the endonuclease and show that incubation of CFS PBMC extracts with 2-5A trimer and tetramer, but not with the dimer, results in a significant protection of the native 83-kDa RNase L against cleavage by endogenous and purified proteases. Similar results are obtained with a purified recombinant RNase L. An analysis of the size of 2-5A oligomers produced by the catalytic activity of the 2-5A synthetase present in PBMC extracts further shows that samples containing the 37-kDa RNase L preferentially produce 2-5A dimers instead of higher oligomers. Taken together, our results indicate that homodimerization of RNase L by 2-5A oligomers higher than the dimer prevents its cleavage by proteolytic enzymes. The presence of the truncated 37-kDa RNase L in PBMC extracts is therefore likely to result, not only from the abnormal activation of inflammatory proteases, but also from a dysregulation in 2-5A synthetase induction or activation towards the preferential production of 2-5A dimers.

Study Objective: To examine whether bronchial hyperresponsiveness (BHR) in patients with chronic fatigue syndrome (CFS) is caused by immune system abnormalities., Design: Prospective comparative study., Setting: A university-based outpatient clinic (Vrije Universiteit; Brussels, Belgium)., Participants: One hundred thirty-seven CFS patients and 27 healthy volunteers., Measurements: Pulmonary function testing, histamine bronchoprovocation test, immunophenotyping, and ribonuclease (RNase) latent determination., Results: Seventy-three of 137 patients presented with BHR, of whom 64 had normal results of the histamine bronchoprovocation test. No significant differences were found in age or sex characteristics between the groups. There were no differences in the RNase L ratio, total lung capacity, or FEV(1)/FVC ratio between CFS patients with or without BHR. The group of patients in whom BHR was present (BHR+) differs most significantly from the control group with eight differences in the immunophenotype profile in the cell count analysis and seven differences in the percentage distribution profile. The group of patients in whom no BHR was detected (BHR-) only differed from the control subjects in CD25+ count and in the percentage of CD25+ cells. We observed a significant increase in cytotoxic T-cell count and in the percentage of BHR+ patients compared to BHR- patients, which is consistent with the significant reduction in percentage naïve T cells., Conclusions: These results refute any association between the cleaving of 80 kd RNase L and BHR. Immunophenotyping of our sample confirmed earlier reports on (chronic) immune activation in patients with CFS, compared to healthy control subjects. BHR+ CFS patients have more evidence of immune activation compared to BHR- patients. Inflammation and the consequent IgE-mediated activation of mast cells and eosinophils, as seen in asthma patients, is unlikely to be responsible for the presence of BHR in patients with CFS.