Impaired remyelination in mixed active/inactive multiple sclerosis lesions
ECTRIMS Online Library. Heß K. 09/13/19; 278448; P1245
Katharina Heß
Katharina Heß
Contributions
Abstract

Abstract: P1245

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms

K. Heß, T. Kuhlmann

Institute of Neuropathology, University of Muenster, Münster, Germany

Due to so far unknown reasons, the capacity of remyelination in Multiple Sclerosis (MS) lesions decreases over the course of the disease. It has been shown that immune cells can influence oligodendroglial differentiation and that timed coordination of particular macrophage phenotypes and functions are essential for efficient remyelination.
Therefore the aim of our study is to examine the relationship between inflammation and remyelination by correlating the extent of remyelination with inflammatory lesion activity as well as the expression of different macrophage and microglia markers in lesions with and without remyelination. To address this question we analysed a collection of more than 260 tissue samples from 78 patients by immunohistochemistry (IHC) for i) different myelin proteins and macrophage markers, ii) determined the extent of remyelination with respect to inflammatory lesion activity and iii) quantified the percentage of different macrophage and microglia subpopulations using markers such as TMEM119, Iba1, CD206, CD163, iNOS as well as oligodendrocytes (IHC for Olig2, NogoA, BCAS).
Mixed active/inactive MS lesions (MLs) showed significantly less remyelination than active (ALs) and inactive lesions (ILs). Whereas ILs as well as ALs presented a heterogeneous distribution of remyelination, all MLs were characterized by no or only limited remyelination. However, as reported earlier, subcortical lesions showed a higher proportion of lesions with marked remyelination compared to periventricular and cerebellar lesions.
Assessing the inflammatory infiltrate, we found a significant higher percentage of CD68+ macrophages/microglia cells expressing TMEM119+ or iNOS+ in the rim of MLs compared to ALs. There were significantly less TMEM119+ and iNOS+ cells in lesions with marked remyelination compared to lesions with no or little remyelination. Analyzing the distribution of oligodendroglial markers, significantly more Olig2+ cells where seen in lesions with marked remyelination compared to lesions with no or little remyelination.
Together, our data demonstrate significantly impaired remyelination in MLs which is associated with predominance of certain macrophage/microglia subpopulations, suggesting that the inflammatory milieu may contribute to remyelination failure in MS. Further studies are required to identify molecular pathways participating in this non-permissive remyelination environment which might pave the way for new treatment options.
Disclosure: K.H. is supported by a fellowship from the Hertie Foundation.
T.K. received honoraria for lectures from Novartis and EXCEMED and funding from the German Research Foundation, the National MS Society, the European Leukodystrophy Association and the Progressive MS Alliance. This study is supported by the Hertie Foundation.

Abstract: P1245

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms

K. Heß, T. Kuhlmann

Institute of Neuropathology, University of Muenster, Münster, Germany

Due to so far unknown reasons, the capacity of remyelination in Multiple Sclerosis (MS) lesions decreases over the course of the disease. It has been shown that immune cells can influence oligodendroglial differentiation and that timed coordination of particular macrophage phenotypes and functions are essential for efficient remyelination.
Therefore the aim of our study is to examine the relationship between inflammation and remyelination by correlating the extent of remyelination with inflammatory lesion activity as well as the expression of different macrophage and microglia markers in lesions with and without remyelination. To address this question we analysed a collection of more than 260 tissue samples from 78 patients by immunohistochemistry (IHC) for i) different myelin proteins and macrophage markers, ii) determined the extent of remyelination with respect to inflammatory lesion activity and iii) quantified the percentage of different macrophage and microglia subpopulations using markers such as TMEM119, Iba1, CD206, CD163, iNOS as well as oligodendrocytes (IHC for Olig2, NogoA, BCAS).
Mixed active/inactive MS lesions (MLs) showed significantly less remyelination than active (ALs) and inactive lesions (ILs). Whereas ILs as well as ALs presented a heterogeneous distribution of remyelination, all MLs were characterized by no or only limited remyelination. However, as reported earlier, subcortical lesions showed a higher proportion of lesions with marked remyelination compared to periventricular and cerebellar lesions.
Assessing the inflammatory infiltrate, we found a significant higher percentage of CD68+ macrophages/microglia cells expressing TMEM119+ or iNOS+ in the rim of MLs compared to ALs. There were significantly less TMEM119+ and iNOS+ cells in lesions with marked remyelination compared to lesions with no or little remyelination. Analyzing the distribution of oligodendroglial markers, significantly more Olig2+ cells where seen in lesions with marked remyelination compared to lesions with no or little remyelination.
Together, our data demonstrate significantly impaired remyelination in MLs which is associated with predominance of certain macrophage/microglia subpopulations, suggesting that the inflammatory milieu may contribute to remyelination failure in MS. Further studies are required to identify molecular pathways participating in this non-permissive remyelination environment which might pave the way for new treatment options.
Disclosure: K.H. is supported by a fellowship from the Hertie Foundation.
T.K. received honoraria for lectures from Novartis and EXCEMED and funding from the German Research Foundation, the National MS Society, the European Leukodystrophy Association and the Progressive MS Alliance. This study is supported by the Hertie Foundation.

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