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Neuroinflammation and demyelination in multiple sclerosis after allogeneic hematopoietic stem cell transplantation
Jian-Qiang Lu1, Jeffrey T Joseph, Richard A Nash
1Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
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.
Design:
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.
Setting:
Referral centers. Intervention Allogeneic hematopoietic stem cell transplantation.
Main Outcome Measures:
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.
Conclusion:
Allo-HSCT fails to halt the demyelination and inflammation of MS.
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