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Purpose: The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory,co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TMand the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. Materials and Methods: Intraabdominal transplant of cardiac allografts from BALB/c (H-2d) donors to C57BL/6 (H-2b) recipientswas performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitonealroute until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells andspleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assayon day 7. Results: The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DXtreatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4+FOXP3+/CD4+CD44hi Tcell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+CD85k+ with TM/DX were observed. Theinhibition of pro-inflammatory cytokine interleukin-6 was also observed. Conclusion: These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survivalby inducing tolerance in transplantation.
The shortage of donor organs is one of the major barriers of transplantation worldwide. After the success of the direct exchange donor (swap) program in Korea since 1991, a swaparound program has been developed. Recently, a web-based (computerized) algorithm to facilitate donor kidney exchange was devised and tested in multi-center settings. An excellent longterm outcome was achieved by using the donor exchange program as an option to reduce the donor organ shortage. Herein, we discussed on the current status of the exchange donor renal transplantation in Korea, a couple of problems we have had, and future directions we have to head and make better to improve organ donation activities.
Purpose: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatmentsuch as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences whenbortezomib was used to treat refractory AMR. Materials and Methods: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients receivedone or two cycles of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11. Results: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I andII, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMRepisodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months aftertherapy (36.91±22.15 mL/min/1.73 m2) versus eGFR at time of AMR diagnosis (17.00±9.25 mL/min/1.73 m2; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three ofthe five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function. Conclusion: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by varioustypes of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.