Neuroinflammation and demyelination in multiple sclerosis after allogeneic hematopoietic stem cell transplantation

Arch Neurol. 2010 Jun;67(6):716-22. doi: 10.1001/archneurol.2010.117.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amyloid beta-Protein Precursor / metabolism
  • Antigens, CD / classification
  • Antigens, CD / metabolism
  • Case-Control Studies
  • Demyelinating Diseases / pathology*
  • Encephalitis / pathology*
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Multiple Sclerosis / surgery*
  • Postmortem Changes
  • Statistics, Nonparametric
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Transplantation, Homologous / adverse effects*

Substances

  • Amyloid beta-Protein Precursor
  • Antigens, CD