Study – The Role of Iron in MS
The role of iron dysregulation in the pathogenesis of multiple sclerosis: an Egyptian study.
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
9 patients were relapsing and progressive (secondary progressive (SP) of which
6 were secondary progressive active (SP-A) and
3 were secondary progressive stable (SP-S)), seven were relapsing-remitting active (RR-A) and
4 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.
Department of Neurology,
Cairo University,
Cairo, Egypt.