Department of Neurology, Cairo University, Cairo, Egypt.
Background Iron
is essential for virtually all types of cells and organisms. The significance of
iron for brain function is reflected by the presence of receptors for
transferrin on brain capillary endothelial cells. Iron imbalance is associated
with proinflammatory cytokines and oxidative stress, which have been implicated
in the pathogenesis of multiple sclerosis (MS). Transferrin receptor (TfR) is
the major mediator of iron uptake. Its expression is increased to facilitate
iron entrance into the cell. The increased serum level of soluble transferrin
receptor (sTfR) may indicate an abnormal intracellular distribution of iron and
a decrease in the cytoplasmic compartment. Objective Our objective is to assess
the possible role of iron metabolism dysfunction in the pathogenesis of MS.
Methods Thirty subjects were selected from the Neurology Department of Kasr
El-Aini hospital, Cairo University: 20 MS patients, where nine patients were
relapsing and progressive (secondary progressive (SP) of which six were
secondary progressive active (SP-A) and three were secondary progressive stable
(SP-S)), seven were relapsing-remitting active (RR-A) and four were primary
progressive (PP); and 10 control subjects matched in age and sex. Each patient
was subjected to a thorough general medical and neurological examination,
Kurtzke MS rating scales, laboratory assessment, neuro-imaging, evoked
potentials and quantitative determination of the indices of iron metabolism,
such as serum iron and sTfR. Results The serum level of sTfR was significantly
higher in our MS patients compared with the control group (p = 0.0001). The
levels were significantly higher in SP-A (p = 0.001), SP-S (p = 0.01), RR-A (p =
0.0001) and PP (p = 0.003) patients than in controls. Iron values were within
normal limits in all patients. The increased serum sTfR level in non-anemic MS
patients with active disease reflects the increased iron turnover. The elevation
of sTfR levels in stable patients may indicate active inflammation with ongoing
oxidative damage that is not detectable by history or examination. Conclusions
Iron overload and upregulation of iron-handling proteins, such as TfR, in the MS
brain can contribute to pathogenesis of Multiple Sclerosis and iron imbalance is
associated with a prooxidative stress and a proinflammatory environment, this
suggest that iron could be a target for MS therapy to improve neuronal iron
metabolism.
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