Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis.
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.
Metz
Imke
I
Department of Neuropathology, Georg August University, Göttingen, Germany.
Lucchinetti
Claudia F
CF
Openshaw
Harry
H
Garcia-Merino
Antonio
A
Lassmann
Hans
H
Freedman
Marc S
MS
Atkins
Harold L
HL
Azzarelli
Biagio
B
Kolar
Oldrich J
OJ
Brück
Wolfgang
W
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