Контроль гіпотетичного прояву хронічного синдрому втоми: попередні спостереження

Whole body potassium measurement by gamma-ray spectrometry was used. Several investigators have found this technique to be highly reliable (8, 10). This technique is also successfully used to assess body composition, for example fat-free mass in a validation-study by Schaefer and colleagues (9). However, this method has some drawbacks. Firstly, the entire potassium content of the body is not indicative of any form of potassium-distribution within the different tissues and parts of the body, and within intracellular and extra-cellular compartments. Whilst > 95% of potassium is found intra-cellularly the normal whole body potassium value does not assess hypo- or hyperkalaemia, which is the result of redistribution of intra- and extra-cellular levels and not indicative of a change in whole body levels. Therefore, we would suggest that whole body potassium measurement is insufficient to monitor a channelo-pathy, especially in a complex disorder like CFS. In this study we tried to gain an insight into the variation between intra-cellular and serum potassium levels by calculating the non-serum potassium levels and the ratio of serum potassium to non-serum potassium levels. The serum potassium level did not correlate with the whole body or non-serum levels. The higher the level of serum potassium in relationship to the non-serum potassium levels was considered to be a potential indicator of a channelopathy.

These results confirm earlier reports on high prevalence of a deregulated 2-5A synthetase RNase L antiviral pathway in peripheral mononuclear cells of Chronic Fatigue Syndrome patients (3, 11). Elastases and calpain (36) cleave high molecular weight ribonuclease L (80 kDa) into low molecular weight RNase L (37 kDa). Starting from the N-ter-minal end of the RNase L polypeptide, the first 330 amino acid sequence presents a high degree of homology with the ankyrin repeat motif. Proteolytic cleavage of 80 kDa RNase L generates ankyrin repeat motif-containing fragments. Ankyrins are a family of proteins that control numerous physiological processes by means of interactions with integral membrane proteins. For instance, ankyrin proteins are capable of associating with ABC transporters (13). In addition, since the RNase L-inhibitor (RLI) impairs the 2-5 A binding to RNase L (14), RLI is almost certain to interact with the ankyrin-like part of RNase L (the 2-5 A binding site is located in the ankyrin-like domain). RLI takes part of the ATP binding cassette (ABC) superfamily. Consequently, RLI binds ankyrin-like fragments in CFS-patients. When the ankyrin fragment of RNase L is released by cleavage, it interacts with the ABC-ankyrin domain interaction and deregulation of proper ABC transporters function is inevitable. Recent research revealed sequence similarity between RLI and several ABC transporters, for instance sulfonylurea receptor (SUR 1)  (4). SUR 1 is an important member of ATP-sensitive potassium channels. Whilst impairment of SUR 1 functioning could be postulated to lead to extreme losses of cellular potassium, this was not ment) and calcium influx might have activated T-cells. Indeed, entrance of Ca2+ from the external milieu is required for T-lymphocyte activation with consequent interleukin (IL) -2 production (23-25). In addition, a recent report suggests a modification of the potassium composition of the extra-cellular milieu might be involved in activation of IL-lp (16). Indeed, K+ efflux is a crucial coupling factor in IL-ip-converting enzyme-activation. Increased levels of IL-1 have been reported in several Chronic Fatigue Syndrome samples (19, 20). However, there are just as many reports of normal values of this pro-inflammatory cytokine in CFS patients (21, 22). We can conclude that at least a subset of CFS patients, or a particular stage in the disease process, is characterized by increasing levels of IL-1. We suggest this is the same subset of CFS patients who present with a channelopathy (due to the deregulated antiviral pathway). IL-1 is capable of stimulating nearly all types of humoral and cellular immune responses.

We need to interpret these results with caution. Indeed, sample size was insufficient and most of our patients were tertiary referrals. This sample was not randomly selected. However, consecutive allocation of patients seeking care must be sufficient in preventing selection-bias. RNase L-ratio, erythrocyte sedimentation rate, serum electrolytes and whole body potassium content were determined in the control subjects. In addition, current technology fails to measure intracellular potassium and calcium levels, which leaves us with indirect monitoring of channelopathy.

These observations provide preliminary evidence for a channelopathy in an subset of Chronic Fatigue Syndrome patients. To our knowledge this is the first attempt to monitor channelopathy in CFS, using electrolytes, whole body potassium, RNase L-ratio and immune cell parameters. Future research should address at calcium homeostasis and RNase L-ratio with other aspects of the disease process, to further explore channelopathy in Chronic Fatigue Syndrome.

 

 

Holmes G, Kaplan J, Gantz J, et al. Chronic Fatigue Syndrome: a working case