Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome

J Clin Lab Immunol. 1998;50(1):1-16.


Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) is a disorder characterized by debilitating fatigue associated with immunological abnormalities and cognitive impairments. The recently cloned RNase L Inhibitor (RLI) gene encodes a specific protein which is believed to regulate 2-5A synthetase and RNase L activity via the formation of a latent heterodimeric protein complex. In the present study, we investigated the levels of 2-5A synthetase, RNase L and RLI in patients with CFIDS as compared to healthy controls. Quantitative Competitive PCR (Q/C PCR) analysis showed a statistically significant decrease in RLI mRNA present in the peripheral blood lymphocytes (PBL) of patients with CFIDS (n = 25, mean = 569, S.E = 154) as compared to RLI mRNA level present in peripheral blood lymphocytes (PBL) of healthy controls (n = 15, mean = 2296, S.E = 506; p < 0.0001). The decrease in RLI mRNA in CFIDS individuals correlated directly with RLI and RLI: RNase L protein ratio while showing an inverse relationship to the 2-5A synthetase and RNase L activity. This RLI mRNA and protein deficiency in CFIDS patients may explain the increase in activity of RNase L found in CFIDS patients. The unidirectional decrease in RLI message and protein levels in CFIDS individuals may contribute to the destabilization of the latent RLI:RNase L heterodimeric protein complex, resulting in the excessive activation of RNase L shown in this study. The increased activation of RNase L may result in an increased cellular RNA turnover and subsequent inhibition of protein synthesis; thus resulting in general fatigue, myalgia muscle weakness and other symptomatologies shown in CFIDS patients. Furthermore, this data supports the hypothesis that the antiviral 2-5 oligoadenylate synthetase (2-5OAS) overexpression in individuals with CFIDS correlates with an increase in RNase L activity and with a decrease in RNase L inhibitor.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / blood*
  • ATP-Binding Cassette Transporters*
  • Adult
  • Aged
  • Chaperonins*
  • Down-Regulation
  • Endoribonucleases / blood*
  • Fatigue Syndrome, Chronic / blood*
  • Fatigue Syndrome, Chronic / physiopathology
  • Female
  • Humans
  • Interferons / metabolism
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Proteins / metabolism*
  • RNA, Messenger / analysis
  • Up-Regulation


  • ABCE1 protein, human
  • ATP-Binding Cassette Transporters
  • Proteins
  • RNA, Messenger
  • Interferons
  • 2',5'-Oligoadenylate Synthetase
  • Endoribonucleases
  • 2-5A-dependent ribonuclease
  • Chaperonins