Monitoring a Hypothetical Channelopathy in Chronic Fatigue Syndrome: Preliminary Observations J of Chronic Fatigue Syndrome, Vol. 11(1) 2003 Jo Nijs, MSc; Christian Demanet, MD, PhD; Neil R. McGregor, BDS, MDSc, PhD; Pascale De Becker, PhD; Michel Verhas, MD, PhD; Patrick Englebienne, PhD; Kenny De Meirleir, MD, PhD Jo Nijs and Pascale De Becker are affiliated with the Department of Human Physiology, Faculty of Physical Education and Physical Therapy, Vrije Universiteit Brussel, Belgium. Christian Demanet is affiliated with the Division of Hematology and Immunology, Academic Hospital, Vrije Universiteit Brussel, Belgium. Neil R. McGregor is affiliated with the Collaborative Pain Research Unit, Depart- ment of Biological Sciences, Faculty of Science, University of Newcastle, Callaghan, New South Wales, Australia. Michel Verhas and Patrick Englebienne are affiliated with the Department of Nuclear Medicine, Brugmann Hospital/Academic Hospital. Vrije Universiteit Brussel and Universite Libre Bruxelles (V.U.B-U.L.B.), Brussels, Belgium. Kenny De Meirleir is affiliated with the Department of Human Physiology, Faculty of Physical Education and Physical Therapy, and the Fatigue Clinic, Vrije Universiteit Brussel, Belgium. Address correspondence to: Jo Nijs, Vakgroep MFYS, AZ-VUB KRO gebouw-1, Laarbeeklaan 101, 1090 Brussel-Belgium (E-mail: mailto:Jo.Nijs@vub.ac.be ). ABSTRACT. This study was 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, percent 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 CDI9+ CD5+ (mature B-) cells and the decrease in CD3- CDI6+ CDS6+ (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 suggest a channelopathy in a subset of CFS patients, probably induced by the deregulated 2-5A RNase L antiviral pathway. KEYWORDS. Chronic fatigue syndrome, channelopathy, immunity, RNase L, potassium INTRODUCTION . Chronic Fatigue Syndrome is characterized by numerous symptoms, but there does not appear to be a single underlying cause for all patients. Indeed, Holmes (1988) (1) and Fukuda (1994) (2) CDC-criteria gave rise to a heterogeneous patient-group. This heterogeneity therefore re- quires the investigators to delineate those features that may be causative as compared to those features that may result from secondary host responses or co-morbid disease. There is a growing international consensus to differentiating Chronic Fatigue Syndrome into clinically relevant subcategories that may represent either different disease states or to differentiate the potential co- morbid illnesses. Therefore, assessment of the deregulation of the 2-5A synthetase/RNase L antiviral pathway (3) and its associations with biochemical, immune and symptom changes is of prime importance. A recent report (4) suggests possible associations between the deregulated pathway and a channelopathy (5,6,7) in chronic fatigue syndrome. Thus an assessment of the associations between the RNase L-ratio and electrolyte changes may allow determination of any association between RNase L-anomaly and a potential channelopathy as assessed by a serum electrolyte panel and whole body potassium determination. We present here a study of a small sample of CFS patients (and matched healthy controls) in which we use uni- and multivariate analyses to assess any possible associations between the RNase L-ratio, electrolytes, biochemical and immunological parameters. © 2003 by The Haworth Press, Inc. All rights reserved.