Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease: Implication for disease pathogenesis

Iliana Michailidou, Daphne M.P. Naessens, Simon Hametner, Willemijn Guldenaar, Evert Jan Kooi, Jeroen J.G. Geurts, Frank Baas, Hans Lassmann, Valeria Ramaglia

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Microglial clusters with C3d deposits are observed in the periplaque of multiple sclerosis (MS) brains and were proposed as early stage of lesion formation. As such they should appear in the brain of MS donors with acute disease but thus far this has not been shown. Using postmortem brain tissue from acute (n = 10) and chronic (n = 15) MS cases we investigated whether C3d+ microglial clusters are part of an acute attack against myelinated axons, which could have implications for disease pathogenesis. The specificity of our findings to MS was tested in ischemic stroke cases (n = 8) with initial or advanced lesions and further analyzed in experimental traumatic brain injury (TBI, n = 26), as both conditions are primarily nondemyelinating but share essential features of neurodegeneration with MS lesions. C3d+ microglial clusters were found in chronic but not acute MS. They were not associated with antibody deposits or terminal complement activation. They were linked to slowly expanding lesions, localized on axons with impaired transport and associated with neuronal C3 production. C3d+ microglial clusters were not specific to MS as they were also found in stroke and experimental TBI. We conclude that C3d+ microglial clusters in MS are not part of an acute attack against myelinated axons. As such it is unlikely that they drive formation of new lesions but could represent a physiological mechanism to remove irreversibly damaged axons in chronic disease. GLIA 2017;65:264–277.

Original languageEnglish
Pages (from-to)264-277
Number of pages14
JournalGLIA
Volume65
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Cite this

Michailidou, Iliana ; Naessens, Daphne M.P. ; Hametner, Simon ; Guldenaar, Willemijn ; Kooi, Evert Jan ; Geurts, Jeroen J.G. ; Baas, Frank ; Lassmann, Hans ; Ramaglia, Valeria. / Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease : Implication for disease pathogenesis. In: GLIA. 2017 ; Vol. 65, No. 2. pp. 264-277.
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title = "Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease: Implication for disease pathogenesis",
abstract = "Microglial clusters with C3d deposits are observed in the periplaque of multiple sclerosis (MS) brains and were proposed as early stage of lesion formation. As such they should appear in the brain of MS donors with acute disease but thus far this has not been shown. Using postmortem brain tissue from acute (n = 10) and chronic (n = 15) MS cases we investigated whether C3d+ microglial clusters are part of an acute attack against myelinated axons, which could have implications for disease pathogenesis. The specificity of our findings to MS was tested in ischemic stroke cases (n = 8) with initial or advanced lesions and further analyzed in experimental traumatic brain injury (TBI, n = 26), as both conditions are primarily nondemyelinating but share essential features of neurodegeneration with MS lesions. C3d+ microglial clusters were found in chronic but not acute MS. They were not associated with antibody deposits or terminal complement activation. They were linked to slowly expanding lesions, localized on axons with impaired transport and associated with neuronal C3 production. C3d+ microglial clusters were not specific to MS as they were also found in stroke and experimental TBI. We conclude that C3d+ microglial clusters in MS are not part of an acute attack against myelinated axons. As such it is unlikely that they drive formation of new lesions but could represent a physiological mechanism to remove irreversibly damaged axons in chronic disease. GLIA 2017;65:264–277.",
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author = "Iliana Michailidou and Naessens, {Daphne M.P.} and Simon Hametner and Willemijn Guldenaar and Kooi, {Evert Jan} and Geurts, {Jeroen J.G.} and Frank Baas and Hans Lassmann and Valeria Ramaglia",
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Michailidou, I, Naessens, DMP, Hametner, S, Guldenaar, W, Kooi, EJ, Geurts, JJG, Baas, F, Lassmann, H & Ramaglia, V 2017, 'Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease: Implication for disease pathogenesis' GLIA, vol. 65, no. 2, pp. 264-277. https://doi.org/10.1002/glia.23090

Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease : Implication for disease pathogenesis. / Michailidou, Iliana; Naessens, Daphne M.P.; Hametner, Simon; Guldenaar, Willemijn; Kooi, Evert Jan; Geurts, Jeroen J.G.; Baas, Frank; Lassmann, Hans; Ramaglia, Valeria.

In: GLIA, Vol. 65, No. 2, 01.02.2017, p. 264-277.

Research output: Contribution to journalArticleAcademicpeer-review

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T2 - Implication for disease pathogenesis

AU - Michailidou, Iliana

AU - Naessens, Daphne M.P.

AU - Hametner, Simon

AU - Guldenaar, Willemijn

AU - Kooi, Evert Jan

AU - Geurts, Jeroen J.G.

AU - Baas, Frank

AU - Lassmann, Hans

AU - Ramaglia, Valeria

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N2 - Microglial clusters with C3d deposits are observed in the periplaque of multiple sclerosis (MS) brains and were proposed as early stage of lesion formation. As such they should appear in the brain of MS donors with acute disease but thus far this has not been shown. Using postmortem brain tissue from acute (n = 10) and chronic (n = 15) MS cases we investigated whether C3d+ microglial clusters are part of an acute attack against myelinated axons, which could have implications for disease pathogenesis. The specificity of our findings to MS was tested in ischemic stroke cases (n = 8) with initial or advanced lesions and further analyzed in experimental traumatic brain injury (TBI, n = 26), as both conditions are primarily nondemyelinating but share essential features of neurodegeneration with MS lesions. C3d+ microglial clusters were found in chronic but not acute MS. They were not associated with antibody deposits or terminal complement activation. They were linked to slowly expanding lesions, localized on axons with impaired transport and associated with neuronal C3 production. C3d+ microglial clusters were not specific to MS as they were also found in stroke and experimental TBI. We conclude that C3d+ microglial clusters in MS are not part of an acute attack against myelinated axons. As such it is unlikely that they drive formation of new lesions but could represent a physiological mechanism to remove irreversibly damaged axons in chronic disease. GLIA 2017;65:264–277.

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