Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic stem cell transplantation (allo SCT) is now frequently performed for the treatment of haematological malignancies and aplastic anaemia. However, graft-versus-host disease (GVHD) is still the major complication after allo SCT, producing immune deficiency, infection, organ damage and, occasionally, patient death. The antigen-specific signal mediated by the T-cell receptor (TCR) is essential for activation of T-cells; however, additional co-stimulatory signals are required for complete T-cell activation. Therefore, blocking strategies of co-stimulatory signals have been evaluated as targets of therapeutic intervention for GVHD after allo SCT. In a mouse bone-marrow transplantation (BMT) model, the administration of CTLA4-Ig, which blocks the interaction of CD28 on T-cells and B7 molecules on antigen-presenting cells (APCs), can prolong survival of allo BMT recipients, although this effect was not complete. In addition, the anti-CD40L (CD154) monoclonal antibody (mAb), which can interfere with the interaction of CD154 on T-cells and CD40 on APCs, can induce long-term graft survival in the murine model. Combined administration of CTLA4-Ig and anti-CD40L mAb can prevent allograft rejection in primates. Therefore, it seems the most powerful method to prevent the alloimmune response in vivo. The Fas/Fas ligand pathway is also involved in pathogenesis of GVHD. Anti-FasL mAb can reduce the mortality of GVHD and improve intestinal lesions. Recently, it was reported that donor bone marrow treated ex vivo using CTLA4-Ig reconstituted haematopoiesis in vivo with a relatively low risk of GVHD in human allo BMT. Therefore, selective blocking strategies for T-cell co-signalling might be useful for the prevention of GVHD in human allo SCT.
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PMID:T-cell co-signalling molecules in graft-versus-host disease. 1090 5

CD40 ligand, a 33-kDa cell membrane molecule, a member of the tumor necrosis factor superfamily, is an important costimulatory molecule during immune response. Here, we report on two functional mouse anti-human CD40L monoclonal antibodies 1B1 and 4F1 characterized by flow cytometry, Western blotting, and competition assay. The antibodies bound to distinct CD40L epitopes and therefore resulted in different bioactivity. Both antibodies could induce CD4+ T-cell alloantigenic hyporesponsiveness ex vivo. The antibodies were matched to develop a two-site enzyme-linked immunosorbent assay (ELISA) for soluble CD40L (sCD40L). Using this ELISA assay, we found major differences between plasma and serum sCD40L levels. Because the count of platelet sharply decreased in aplastic anemia (AA) and idiopathic thrombocytopenic purpura (ITP), we further analyzed the sCD40L concentration in the plasma of AA and ITP patients. The results showed that the sCD40L in serum was much lower than that of healthy subjects. These data demonstrate that platelets seem to be a major contributor to sCD40L, though not the only source of sCD40L in serum.
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PMID:Characterization and application of two novel monoclonal antibodies against CD40L: epitope and functional studies on cell membrane CD40L and studies on the origin of soluble serum CD40L. 1530 6