Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis

Imke Metz, Claudia F Lucchinetti, Harry Openshaw, Antonio Garcia-Merino, Hans Lassmann, Marc S. Freedman, Harold L. Atkins, Biagio Azzarelli, Oldrich J. Kolar, Wolfgang Brück

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The present study analyses autopsy material from five multiple sclerosis patients who received autologous stem cell transplantation. A total of 53 white matter lesions were investigated using routine and immunohistochemical stainings to characterize the demyelinating activity, inflammatory infiltrates, acutely damaged axons and macrophages/microglial cells. We found evidence for ongoing active demyelination in all of the five patients. The inflammatory infiltrate within the lesions showed only very few T cells and CD8+ cytotoxic T cells dominated the T cell population. B cells and plasma cells were completely absent from the lesions. High numbers of acutely damaged axons were found in active lesion areas. Tissue injury was associated with activated macrophages/microglial cells. The present results indicate that ongoing demyelination and axonal degeneration exist despite pronounced immunosuppression. Our data parallel results from some of the clinical phase I/II studies showing continued clinical disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous stem cell transplantation.

Original languageEnglish (US)
Pages (from-to)1254-1262
Number of pages9
JournalBrain
Volume130
Issue number5
DOIs
StatePublished - May 2007

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Hematopoietic Stem Cell Transplantation
Demyelinating Diseases
Multiple Sclerosis
Stem Cell Transplantation
T-Lymphocytes
Axons
Macrophages
Plasma Cells
Immunosuppression
Disease Progression
Autopsy
B-Lymphocytes
Staining and Labeling
Wounds and Injuries
Population

Keywords

  • Demyelination
  • Multiple sclerosis
  • Neurodegeneration
  • Stem cell transplantation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis. / Metz, Imke; Lucchinetti, Claudia F; Openshaw, Harry; Garcia-Merino, Antonio; Lassmann, Hans; Freedman, Marc S.; Atkins, Harold L.; Azzarelli, Biagio; Kolar, Oldrich J.; Brück, Wolfgang.

In: Brain, Vol. 130, No. 5, 05.2007, p. 1254-1262.

Research output: Contribution to journalArticle

Metz, I, Lucchinetti, CF, Openshaw, H, Garcia-Merino, A, Lassmann, H, Freedman, MS, Atkins, HL, Azzarelli, B, Kolar, OJ & Brück, W 2007, 'Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis', Brain, vol. 130, no. 5, pp. 1254-1262. https://doi.org/10.1093/brain/awl370
Metz, Imke ; Lucchinetti, Claudia F ; Openshaw, Harry ; Garcia-Merino, Antonio ; Lassmann, Hans ; Freedman, Marc S. ; Atkins, Harold L. ; Azzarelli, Biagio ; Kolar, Oldrich J. ; Brück, Wolfgang. / Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis. In: Brain. 2007 ; Vol. 130, No. 5. pp. 1254-1262.
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