AUTOIMMUNITY part 74

Immune 4

 

AUTOLOGOUS  HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)

The ability to adoptively transfer autoimmune diseases with bone marrow transplantation in a variety of animal models provides strong evidence that these disorders are mediated by cells derived from hematopoietic cells. There is compelling evidence that autoimmune disease results from a loss of B- or T-cell tolerance to certain self-antigens. Hematopoietic stem cells are the earliest progenitor cells of the immune system and give rise to B and T lymphocytes as well as antigen-presenting cells (monocytes, macrophages and dendritic cells). The rationale  for HSCT as a therapy for autoimmune disease is based on the concept that the peripheral expansion of autoreactive T- and B-cell clones is central to the pathogenesis of autoimmunity. If these autoantigen-specific cells can be deleted and the immune system regenerated with “normal” hematopoietic stem cells, there is the potential to effect a “cure” of autoimmune disease. Therapy is based on the mobilization of hematopoietic stem cells using C-CSF or G-CSF plus cyclophosphamide. There is the risk during mobilization of flares caused by G-CSF treatment. The stem cells are depleted of lymphocytes and enriched for CD34 cells followed by expansion and reinfusion into the same donor after “conditioning.” The conditioning regimen involves cyclophosphamide treatment or other immunosuppressive treatments aimed at depleting mature lymphocytes. Phase II clinical trials of the efficacy of autologous HSCT in MS, SLE, RA and scleroderma are ongoing or planned. Promising preliminary results have been obtained with all of these conditions, but further study is needed.

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