Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.

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 sign...

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Autores principales:	Veela Mehta, Wei Pei, Grant Yang, Suyang Li, Eashwar Swamy, Aaron Boster, Petra Schmalbrock, David Pitt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c34a63acea62434b82453471df7da67b
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spelling	oai:doaj.org-article:c34a63acea62434b82453471df7da67b2021-11-18T07:53:30ZIron is a sensitive biomarker for inflammation in multiple sclerosis lesions.1932-620310.1371/journal.pone.0057573https://doaj.org/article/c34a63acea62434b82453471df7da67b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516409/?tool=EBIhttps://doaj.org/toc/1932-6203MRI 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. 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. 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. 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.Veela MehtaWei PeiGrant YangSuyang LiEashwar SwamyAaron BosterPetra SchmalbrockDavid PittPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e57573 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Veela Mehta Wei Pei Grant Yang Suyang Li Eashwar Swamy Aaron Boster Petra Schmalbrock David Pitt Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.
description	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. 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. 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. 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.
format	article
author	Veela Mehta Wei Pei Grant Yang Suyang Li Eashwar Swamy Aaron Boster Petra Schmalbrock David Pitt
author_facet	Veela Mehta Wei Pei Grant Yang Suyang Li Eashwar Swamy Aaron Boster Petra Schmalbrock David Pitt
author_sort	Veela Mehta
title	Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.
title_short	Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.
title_full	Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.
title_fullStr	Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.
title_full_unstemmed	Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.
title_sort	iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c34a63acea62434b82453471df7da67b
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Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions.

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