J Nijs,[1,6] PT; C Demanet,  MD, PhD; N McGregor,  MDSc, PhD; P De Becker,  PhD; M Verhas,  MD, PhD; P Englebienne,  PhD; and K De Meirleir, [1,2] MD, PhD
|1: Department of Human Physiology
Faculty of Physical Education and Physical Therapy
Vrije Universiteit Brussel,
|2: Fatigue Clinic
Vrije Universiteit Brussel
|3: Collaborative Pain Research Unit
Department of Biological Sciences
Faculty of Science
University of Newcastle,
Callaghan, New South Wales,
|4: Department of Nuclear Medicine
Brugmann Hospital / Academic Hospital
Vrije Universiteit Brussel and Université Libre Bruxelles (V.U.B - U.L.B.)
|5: Division of Hematology and Immunology
Academic Hospital Vrije Universiteit
|6: To whom correspondence should be addressed:
AZ-VUB KRO gebouw
1, Laarbeeklaan 101, 1090
Monitoring a Hypothetical Channelopathy in Chronic Fatigue Syndrome
This study aimed at monitoring of a previously suggested channelopathy in Chronic Fatigue Syndrome, and at searching for possible explanations by means of immune system characteristics.
Twenty-seven CFS patients and 20 age and sex matched healthy volunteers were recruited. RNase L-ratio, % of the norm of whole body potassium content, serum electrolytes (sodium, calcium and potassium), immune cells, blood cell count and erythrocyte sedimentation rate were determined.
More than fifty percent of our patients presented with abnormal whole body potassium content. Eight patients had increased, while six had depleted potassium content. Discriminant function analysis revealed that the CFS patients and control subjects could be differentiated on immunophenotyping with the predominant cell differences being the increase in CD19+CD5+ (mature B-) cells and the decrease in CD3-CD16+CD56+ (NK) cells in both the percentage and count distributions. The fall in NK-cells was very strongly associated with increases in the RNase L-ratio and falls in serum calcium levels. In addition, four patients with low serum calcium levels showed lower whole body potassium levels.
In conclusion, these observations provide evidence for a channelopathy in an important subset of CFS-patients, probably induced by the deregulated 2,5A RNase L antiviral pathway. Proteolytic cleavage of 80 kDa RNase L generates ankyrin repeat motif-containing fragments. RLI (RNase L inhibitor) takes part of the ATP binding cassette (ABC) superfamily, and is capable of binding ankyrin-like fragments in CFS-patients. Consequently, ankyrin fragments, released by RNase L cleavage, interacts with the ABC-ankyrin domain interaction and deregulation of proper ABC transporters function is inevitable.
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