Research: Iron in Lesions

Epub: Mehta et al. Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions. PLoS One. 2013;8(3):e57573. doi: 10.1371/ journal.pone.0057573.

Background: MRI phase imaging in multiple sclerosis (MS) patients and in autopsy tissue have demonstrated the presence of iron depositions in white matter lesions. The accumulation of iron in some but not all lesions suggests a specific, potentially disease-relevant process, however; its pathophysiological significance remains unknown. 

Objective: HERE, WE EXPLORE THE ROLE OF LESIONAL IRON IN MULTIPLE SCLEROSIS USING MULTIPLE APPROACHES: immunohistochemical examination of autoptic MS tissue, an in vitro model of iron-uptake in human cultured macrophages and ultra-highfield phase imaging of highly active and of secondary progressive MS patients. 

Results: Using Perls’ stain and immunohistochemistry, iron was detected in MS tissue sections predominantly in non-phagocytosing macrophages/microglia at the edge of established, demyelinated lesions. Moreover, iron-containing macrophages but not myelin-laden macrophages expressed markers of proinflammatory (M1) polarization. Similarly, in human macrophage cultures, iron was preferentially taken up by non-phagocytosing, M1-polarized macrophages and induced M1 (super) polarization. Iron uptake was minimal in myelin-laden macrophages and active myelin phagocytosis led to depletion of intracellular iron. Finally, we demonstrated in MS patients using GRE phase imaging with ultra-highfield MRI that phase hypointense lesions were significantly more prevalent in patients with active relapsing than with secondary progressive MS. 

Conclusions: Taken together, our data provide a basis to interpret iron-sensitive GRE phase imaging in MS patients: iron is present in non-phagocytosing, M1-polarized microglia/macrophages at the rim of chronic active white matter demyelinating lesions. Phase imaging may therefore visualize specific, chronic proinflammatory activity in established MS lesions and thus provide important clinical information on disease status and treatment efficacy in MS patients.

The presence of iron depositions was part of the build up to the vascular hypothesis that led to the development of CCSVI. There is no question that there appears to be accumulation of iron in and around MS lesions, this study links it to inflammation and the presence of macrophages/microglia. We have previously monitored ferritin (iron) within lesions and it is known that this can be associated with macrophages/microglia.

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  • I wonder…

    The relationship between iron deposition and MS is described since the 1930's (that the earliest study I have availible in my archive) when they sliced the brain of diseased MSers.

    Why don't we know more about this effect?
    That's 80 years!


  • Why don't we know more about this effect

    Maybe because people think there are more important things to know. I am sure someone with research interest in this aspect would know alot more.

  • Maybe the CCSVI nutters could start proclaiming that wearing a magnetic necklace cures MS. They need a new therapy to devote their hysterics' to.

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