КОНТРОЛЬ ГІПОТЕТИЧНОГО ПРОЯВУ ХРОНІЧНОГО СИНДРОМУ ВТОМИ: ПОПЕРЕДНІ СПОСТЕРЕЖЕННЯ
MONITORING A HYPOTHETICAL CHANNELOPATHY IN CHRONIC FATIGUE SYNDROME: PRELIMINARY OBSERVATIONS
Jo Nijs, Neil R. McGregor, Pascale De Becker, Michel Verhas, Patrick Englebienne, Kenny De Meirleir
Department of Human Physiology, Faculty of Physical Education and Physical Therapy, Vrije Universiteit Brussel, Belgium
Division of Hematology and Immunology, Academic Hospital, Vrije Universiteit Brussel, Belgium
Collaborative Pain Research Unit, Department of Biological Sciences, Faculty of Science, University of Newcastle, Callaghan, New South Wales, Australia
Department of Nuclear Medicine, Brugmann Hospital, Brussels, Belgium
Department of Human Physiology, Faculty of Physical Education and Physical Therapy, and the Fatigue Clinic, Vrije Universiteit Brussel, Belgium
Анотація. Джо Нійс, Дейл Р. Мак Грегор, Паскаль де Беке та ін. Контроль гіпотетичного прояву хронічного синдрому втоми: попередні спостереження. У статті описано дослідження щодо вивчення контролю хронічного синдрому втоми використовуючи дні вмісту в організмі хворого електролітів, калію, RNase L-ratio і імунних параметрів.
Ключові слова: хронічний синдром втоми, організм, імунітет, калій, диференціація.
Аннотация. Джо Нийс, Дейл Р. Мак Грегор, Паскаль где Беке но др. Контроль гипотетического проявления хронического синдрома усталости: предыдущие наблюдения. В статье описано исследование относительно изучения контроля хронического синдрома усталости, используя дни содержания в организме больного электролитов, калию, RNase L-ratio и иммунных параметров.
Ключевые слова: хронический синдром усталости, организм, иммунитет, калий, дифференциация.
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 CD 19+ 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 suggest a channelopathy in a subset of CFS patients, probably induced by the deregulated 2-5A RNase L antiviral pathway.
Key words: Chronic fatigue syndrome, channelopathy, immunity, RNase L, potassium.
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 requires 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.
Study Setting and Sample
The study was conducted in Brussels, at a university-based outpatient clinic (Vrije Universiteit Brussel), and approved by the University hospital ethics committee. We enrolled twenty-seven consecutive patients, seeking care for prolonged fatigue as their major complaint who complied with the Fukuda (2) definition. Patients were also evaluated for eligibility according to the Holmes case definition (1) although this was not used as exclusion-criteria. Twenty age and sex matched healthy volunteers were recruited among college students and hospital employees. Immune cells were counted in the blood samples of the control subjects, RNase L-ratio, erythrocyte sedimentation rate, serum electrolytes and whole body potassium content were determined. Before blood collection, they were questioned about medication-use or illness during the past three months.
The selection and characterisation of the