BACKGROUND: We hypothesized that T-regulatory cells specific for donor alloantigens would protect a renal transplant during partial withdrawal of immunosuppression. METHODS: To test this hypothesis, 32 renal transplant recipients aged 55 years and older with excellent renal function were tested for donor-specific regulation (DSR) by trans-vivo delayed type hypersensitivity assay at the time of enrollment (T=0) and 6 months later (T=6). Twenty-two patients had prednisone withdrawn during a 3-month period, whereas 10 controls were maintained on triple therapy (prednisone, cyclosporine, and mycophenolate). RESULTS:Of 22 patients in the steroid withdrawal group, 10 were DSR+ and 12 were DSR- at the time of enrollment (T=0). None of the DSR+ patients experienced acute rejection, nor did any have donor-specific human leukocyte antigen (HLA) antibody during or after withdrawal. Of 12 DSR- patients, three developed acute rejection, which were reversed with bolus steroid treatment, and four were donor-specific antibody+ at T=0 or T=6. Two years later, 80% (8 of 10) of DSR+ patients in the withdrawal group remain steroid free while maintaining excellent renal function, as compared with only 58% (7 of 12) DSR- patients. Patient survival at 4 years was similar for DSR+ (9 of 10) and DSR- (11 of 12) patients in the withdrawal group. Patients maintained on triple therapy remained rejection free during the 4-year follow-up regardless of initial DSR status, with patient survival rate of 70% (7 of 10). CONCLUSIONS:DSR before steroid withdrawal may identify a subset of transplant patients who could benefit from reduction of immunosuppression without elevated risk of rejection or deteriorating renal function.
RCT Entities:
BACKGROUND: We hypothesized that T-regulatory cells specific for donor alloantigens would protect a renal transplant during partial withdrawal of immunosuppression. METHODS: To test this hypothesis, 32 renal transplant recipients aged 55 years and older with excellent renal function were tested for donor-specific regulation (DSR) by trans-vivo delayed type hypersensitivity assay at the time of enrollment (T=0) and 6 months later (T=6). Twenty-two patients had prednisone withdrawn during a 3-month period, whereas 10 controls were maintained on triple therapy (prednisone, cyclosporine, and mycophenolate). RESULTS: Of 22 patients in the steroid withdrawal group, 10 were DSR+ and 12 were DSR- at the time of enrollment (T=0). None of the DSR+ patients experienced acute rejection, nor did any have donor-specific human leukocyte antigen (HLA) antibody during or after withdrawal. Of 12 DSR- patients, three developed acute rejection, which were reversed with bolus steroid treatment, and four were donor-specific antibody+ at T=0 or T=6. Two years later, 80% (8 of 10) of DSR+ patients in the withdrawal group remain steroid free while maintaining excellent renal function, as compared with only 58% (7 of 12) DSR- patients. Patient survival at 4 years was similar for DSR+ (9 of 10) and DSR- (11 of 12) patients in the withdrawal group. Patients maintained on triple therapy remained rejection free during the 4-year follow-up regardless of initial DSR status, with patient survival rate of 70% (7 of 10). CONCLUSIONS:DSR before steroid withdrawal may identify a subset of transplant patients who could benefit from reduction of immunosuppression without elevated risk of rejection or deteriorating renal function.
Authors: Brian J Nankivell; Richard J Borrows; Caroline L-S Fung; Philip J O'Connell; Richard D M Allen; Jeremy R Chapman Journal: N Engl J Med Date: 2003-12-11 Impact factor: 91.245
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Authors: L D Haynes; E Jankowska-Gan; A Sheka; M R Keller; M P Hernandez-Fuentes; R I Lechler; V Seyfert-Margolis; L A Turka; K A Newell; W J Burlingham Journal: Am J Transplant Date: 2011-12-07 Impact factor: 8.086