title: Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis.
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.
authors.affiliation: Department of Neuropathology, Georg August University, Göttingen, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.forename: Harry
authors.initials: H
authors.lastname: Openshaw
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Merino
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Marc S
authors.initials: MS
authors.lastname: Freedman
authors.forename: Harold L
authors.initials: HL
authors.lastname: Atkins
authors.forename: Biagio
authors.initials: B
authors.lastname: Azzarelli
authors.forename: Oldrich J
authors.initials: OJ
authors.lastname: Kolar
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology; D001921:Brain / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D009186:Myelin Sheath / Q000473:pathology; D009410:Nerve Degeneration; D016612:Paraffin Embedding; D013601:T-Lymphocytes / Q000276:immunology; D014182:Transplantation, Autologous; D017211:Treatment Failure