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Elevated apoptotic cell population in patients with Chronic Fatigue Syndrome (CFS): the pivotal role of protein kinase RNA

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By Vojdani A, Ghoneum M, Choppa PC, Magtoto L, Lapp CW • • December 15, 1997

OBJECTIVES: A prominent feature of chronic fatigue syndrome
(CFS) is a disordered immune system. Recent evidence indicates
that induction of apoptosis might be mediated in a
dysregulated immune system by the upregulation of growth
inhibitory cytokines. Therefore, the purpose of this study was
to evaluate the apoptotic cell population, interferon-alpha
(IFN-alpha) and the IFN-induced protein kinase RNA (PKR) gene
transcripts in peripheral blood lymphocytes (PBL) of CFS
individuals, as compared to healthy controls.

METHODS: PBL were isolated from CFS (n = 29) and healthy
control individuals (n = 15) and subjected to quantitative
analysis of apoptotic cell population and cell cycle
progression by flow cytometry. Quantitative competitive
polymerase chain reaction (Q/C PCR) and Western blot analysis
were used to assess the levels of PKR mRNA and protein in
control and CFS individuals. In addition, circulating
IFN-alpha was measured by ELISA assay.

RESULTS: Increased
apoptotic cell population was observed in CFS individuals, as
compared to healthy controls (26.6 +/- 12.9% and 9.9 +/- 4.2%,
respectively). The increased apoptotic subpopulation in CFS
individuals was accompanied by an abnormal cell arrest in the
S phase and the G2/M boundary of the cell cycle as compared to
the control group (8.6 +/- 1.2 to 22.8 +/- 2.4 and 3.6 +/-
0.82 to 24.3 +/- 3.4, respectively). In addition, CFS
individuals exhibited enhanced PKR mRNA and protein levels
(mean basal level 3538 +/- 1050 and 2.7 +/- 0.26,
respectively) as compared to healthy controls (mean basal
level 562 +/- 162 and 0.89 +/- 0.18, respectively). In 50% of
the CFS samples (n = 29) treated with 2-aminopurine (2-AP) (a
potent inhibitor of PKR) the apoptotic population was reduced
by more then 50%.

CONCLUSIONS: PKR-mediated apoptosis in CFS
individuals may contribute to the pathogenesis and the fatigue
symptomatology associated with CFS.

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