Neuroinflammation and demyelination in multiple sclerosis after allogeneic hematopoietic stem cell transplantation.
OBJECTIVE
To evaluate the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the brains of persons with and without multiple sclerosis (MS) by means of postmortem histopathological examination.


METHODS
Postmortem histopathology, case studies, and case-control studies. Patients Four patients with MS who died at a median of 4.5 months (range, 3-9 months) after allo-HSCT for a concomitant hematologic malignant neoplasm; 5 patients without MS who died at a median of 10.0 months (1-29 months) after allo-HSCT; and 5 control subjects without MS who did not undergo allo-HSCT.


METHODS
Referral centers. Intervention Allogeneic hematopoietic stem cell transplantation.


METHODS
Morphological features and immunohistochemical features, including the quantitative measures of chronic inflammatory cells.


RESULTS
Demyelinating and inflammatory activities of MS persisted after allo-HSCT in all of the patients with MS. Active and chronic active MS lesions exhibited significantly higher numbers of CD3+ T cells and CD8+ cytotoxic T cells and significantly higher scores of CD68+ microglia/macrophages than did chronic inactive lesions or normal-appearing white matter. The normal-appearing brains of allo-HSCT recipients who did not have MS were found to have significantly higher numbers of CD3+ T cells and CD8+ cytotoxic T cells and higher scores of CD68+ microglia/macrophages compared with the controls; however, no demyelination was identified in these non-MS samples.


CONCLUSIONS
Allo-HSCT fails to halt the demyelination and inflammation of MS.
Lu
Jian-Qiang
JQ
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
Joseph
Jeffrey T
JT
Nash
Richard A
RA
Storek
Jan
J
Stevens
Anne M
AM
Metz
Luanne M
LM
Clark
Arthur W
AW
Johnson
Edward S
ES
Yong
V Wee
VW
D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D015703:Antigens, CD / Q000145:classification / Q000378:metabolism; D016022:Case-Control Studies; D003711:Demyelinating Diseases / Q000473:pathology*; D004660:Encephalitis / Q000473:pathology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011180:Postmortem Changes; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous / Q000009:adverse effects*
D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD