Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inability of B and T lymphocytes from mice expressing the lpr mutation to express functional Fas on their cell surface leads to an immunoregulatory defect associated with excessive autoantibody production. Nevertheless, T-dependent antibody response to foreign antigens in these mice appears relatively normal. To better understand exactly how Fas/FasL interactions control autoantibody production, studies were undertaken to determine (1) what kind(s) of B cells are sensitive to Fas-mediated apoptosis and (2) where the autoantibody-producing cells in lpr mice are located. We found that B cells activated by CD40L are extremely sensitive as targets in assays of Th1 CMC. However, B cells that receive a complete signal through their sIgM antigen receptor acquire a FasL-resistant phenotype. In situ analysis of splenic sections from lpr mice demonstrated that autoantibody-producing cells were uniquely localized to the T cell-rich inner PALS. A similar distribution pattern of IgG AFC was found in mice with chronic GVH disease. These data are consistent with the premise that the inner PALS, and not the germinal center, is the major site of FasL regulation of B cell activity and that, as a result of genetic or inducible loss of sensitivity to Fas-mediated apoptosis, autoreactive B cells may survive and differentiate in this location to cause serological autoimmunity.
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PMID:Unique site of autoantibody production in Fas-deficient mice. 918 58

BACKGROUND Graft rejection and graft versus host disease (GvHD) have impeded the success of hematopoietic cell transplantation for severe aplastic anemia (SAA) patients. There is no sufficient data to identify the outcomes of peripheral blood stem cell transplantation (PBSCT) in SAA patients, especially for adult SAA patients. The aim of this study was to evaluate the outcomes of adult SAA patients undergoing PBSCT with the FCA regimen. The FCA regimen includes fludarabine, cyclophosphamide, and anti-thymocyte globulin (ATG). MATERIAL AND METHODS We report our experience with 46 adult SAA patients who underwent PBSCT with the FCA regimen. Thirty SAA patients who received only cyclophosphamide and ATG (CA) regimen were used as controls. Complications and survival outcomes were evaluated and compared. RESULTS There was a significantly higher percentage of patients who achieved >95% donor chimerism by day 30 in the FCA group. The 5-year event-free survival (EFS) rate in the FCA group was higher than that in the CA group (95.4% versus 73.3%). In addition, the 5-year rejection rate (RR) in the FCA group was lower than that in the CA group (4.6% versus 23.6%). A multivariable model identified the FCA regimen as an independent factor affecting EFS and RR. However, GvHD and serious infection did not differ between the 2 groups. For patients with an unrelated donor, the FCA regimen had a higher EFS and a lower RR than the CA regimen. CONCLUSIONS The FCA regimen for PBSCT in adult SAA patients compared favorably to the CA regimen. It can improve EFS and reduce graft rejection, especially for unrelated donor PBSCT.
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PMID:Aplastic Anemia Preconditioned with Fludarabine, Cyclophosphamide, and Anti-Thymocyte Globulin. 3139 50