The role of iron dysregulation in the pathogenesis of multiple sclerosis: an Egyptian study

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.

Our objective is to assess the possible role of iron metabolism dysfunction in the pathogenesis of MS.

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.

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.

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 pro-oxidative stress and a proinflammatory environment, this suggest that iron could be a target for MS therapy to improve neuronal iron metabolism.