Biochemical Dysregulation of the 2-5A Synthetase/RNase L Antiviral Defense Pathway in Chronic Fatigue Syndrome

Abstract

SummaryThe aim of the current study was to examine the biochemical defects in key components of the 2′,5′-oligoadenylate (2-5A) synthe-tase/RNase L antiviral pathway in an extended cohort of patients with chronic fatigue syndrome (CFS) from two sites. CFS patients, who met the CDC criteria for CFS, and matched controls were assessed with respect to their general health, depression, and pain. Biochemical assays were completed for three blood draws over a period of one year. Analysis of the mean values for bioactive 2-5A, RNase L activity, low molecular weight (LMW) RNase L in CFS PBMC extracts confirmed the statistically significant upregulation of the 2-5A synthetase/RNase L pathway compared to control PBMC extracts (p = .001, .002, and .007, respectively). Clinical correlates to the biochemical findings included a negative correlation between Karnofsky Performance Score and bioactive 2-5A (p = .025) or RNase L activity (p = .002) and positive correlation between Metabolic Screening Questionnaire and RNase L activity (p = .01) and between interferon- and LMW RNase L (p = .05). The evidence presented in this study more firmly establishes the dysregulation of the 2-5A synthetase/RNase L pathway in CFS.Key Words: Chronic fatigue syndrome (CFS)2-5ARNase Lantiviral defense pathwayperipheral blood mononuclear cellsinterferon Additional informationNotes on contributorsRobert J. SuhadolnikAt the time of the study, Karen O'Brien was affiliated with Sierra Internal Medicine Associates.