tailieunhanh - Chapter 102. Aplastic Anemia, Myelodysplasia, and Related Bone Marrow Failure Syndromes (Part 6)

Immune-Mediated Injury The recovery of marrow function in some patients prepared for bone marrow transplantation with antilymphocyte globulin (ALG) first suggested that aplastic anemia might be immune-mediated. Consistent with this hypothesis was the frequent failure of simple bone marrow transplantation from a syngeneic twin, without conditioning cytotoxic chemotherapy, which also argued both against simple stem cell absence as the cause and for the presence of a host factor producing marrow failure. Laboratory data support an important role for the immune system in aplastic anemia. Blood and bone marrow cells of patients can suppress normal hematopoietic progenitor cell growth, and removal. | Chapter 102. Aplastic Anemia Myelodysplasia and Related Bone Marrow Failure Syndromes Part 6 Immune-Mediated Injury The recovery of marrow function in some patients prepared for bone marrow transplantation with antilymphocyte globulin ALG first suggested that aplastic anemia might be immune-mediated. Consistent with this hypothesis was the frequent failure of simple bone marrow transplantation from a syngeneic twin without conditioning cytotoxic chemotherapy which also argued both against simple stem cell absence as the cause and for the presence of a host factor producing marrow failure. Laboratory data support an important role for the immune system in aplastic anemia. Blood and bone marrow cells of patients can suppress normal hematopoietic progenitor cell growth and removal of T cells from aplastic anemia bone marrow improves colony formation in vitro. Increased numbers of activated cytotoxic T cells are observed in aplastic anemia patients and usually decline with successful immunosuppressive therapy cytokine measurements show a TH1 immune response interferon y and tumor necrosis factor . Interferon and tumor necrosis factor induce Fas expression on CD34 cells leading to apoptotic cell death localization of activated T cells to bone marrow and local production of their soluble factors are probably important in stem cell destruction. Early immune system events in aplastic anemia are not well understood. Analysis of T cell receptor expression suggests an oligoclonal antigen-driven cytotoxic T cell response. Many different exogenous antigens appear capable of initiating a pathologic immune response but at least some of the T cells may recognize true self-antigens. The rarity of aplastic anemia despite common exposures medicines hepatitis virus suggests that genetically determined features of the immune response can convert a normal physiologic response into a sustained abnormal autoimmune process including polymorphisms in histocompatibility antigens cytokine .