A study of the immunology of the Chronic Fatigue Syndrome (CFS): correlation of immunologic parameters to health dysfunction

Surface and intracellular immunologic and apoptotic markers
and functional lymphocyte assays after stimulation with
anti-CD3/anti-CD28 antibodies or phytohemagglutinin (PHA) were
studied in 44 patients fulfilling the Oxford criteria for
chronic fatigue syndrome (CFS). Results were then correlated
to scores for the Short Form-36 health questionnaire (SF-36),
which assesses eight aspects of patient's well- being, and for
the general health questionnaire (GHQ), which detects current
psychiatric disorder. Patients had significantly increased
mean fluorescence intensity readings of HLA-DR in CD4 and CD8
cells (P < 0.05). Expression of the costimulatory receptor
CD28 in CD8 cells was significantly reduced, and the apoptosis
repressor ratio of bcl-2/bax in both CD4 and CD8 was increased
in patients (P < 0.05). Patients with increased HLA-DR
expression had significantly lower SF-36 total scores, worse
body pains, and poorer general health perception and physical
functioning scores. Increased spontaneous lymphocyte
proliferation was associated with poor general health
perception. PHA proliferative responses were lower in patients
with poor emotional and mental health scores, and the
anti-CD3/anti-CD28 response was low in those with low general
health perception scores. Higher spontaneous proliferation and
reduced PHA responses correlated with higher GHQ scores.
Similarly, GHQ scores were significantly higher, indicating
worse mental health, in those with lower total SF-36 scores
and worse general and mental health scores in the SF-36
questionnaire. Finally, higher expression of the costimulatory
molecule CD28 correlated with higher total SF-36 scores,
general health perception and social functioning scores, and
with lower role limitation due to physical health. The
increased expression of class II antigens and the reduced
expression of the costimulatory receptor CD28, which is a
marker of terminally differentiated cells, lend further
support to the concept of immunoactivation of T- lymphocytes
in CFS and may be consistent with the notion of a viral
etiopathogenesis in the illness. We report, for the first
time, increased expression of the apoptosis repressor protein
bcl-2, which may contribute to enhanced survival of activated
lymphocytes. Using the SF-36 health assessment questionnaire
and the GHQ, we demonstrated changes in different
immunological parameters, each of which correlated with
particular aspects of disease symptomatology.

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