PMID- 19696637
OWN - NLM
STAT- MEDLINE
DCOM- 20090917
LR  - 20211020
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 88
IP  - 4
DP  - 2009 Aug 27
TI  - Successful reduction of immunosuppression in older renal transplant recipients 
      who exhibit donor-specific regulation.
PG  - 533-41
LID - 10.1097/TP.0b013e3181b0f92f [doi]
AB  - 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      prednisone withdrawn during a 3-month period, whereas 10 controls were maintained 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.
FAU - Jankowska-Gan, Ewa
AU  - Jankowska-Gan E
AD  - Department of Surgery, University of Wisconsin-Madison, School of Medicine and 
      Public Health, Madison, WI, USA.
FAU - Sollinger, Hans W
AU  - Sollinger HW
FAU - Pirsch, John D
AU  - Pirsch JD
FAU - Cai, Junchao
AU  - Cai J
FAU - Pascual, Julio
AU  - Pascual J
FAU - Haynes, Lynn D
AU  - Haynes LD
FAU - Munoz del Rio, Alenjandro
AU  - Munoz del Rio A
FAU - Burlingham, William J
AU  - Burlingham WJ
LA  - eng
GR  - R21 DK077354-02/DK/NIDDK NIH HHS/United States
GR  - 1R21-DK077354-01/DK/NIDDK NIH HHS/United States
GR  - R21 DK077354/DK/NIDDK NIH HHS/United States
GR  - R21 DK077354-01A1/DK/NIDDK NIH HHS/United States
GR  - R01 AI066219/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Acute Disease
MH  - Aged
MH  - Aging/*immunology
MH  - Animals
MH  - Calcineurin Inhibitors
MH  - Female
MH  - Follow-Up Studies
MH  - Graft Rejection/etiology/immunology/prevention & control
MH  - Humans
MH  - Hypersensitivity, Delayed
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Kidney Transplantation/adverse effects/*immunology
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Middle Aged
MH  - Mycophenolic Acid/administration & dosage/analogs & derivatives
MH  - Prednisone/administration & dosage
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Tissue Donors
PMC - PMC2747510
MID - NIHMS131485
EDAT- 2009/08/22 09:00
MHDA- 2009/09/18 06:00
PMCR- 2010/08/27
CRDT- 2009/08/22 09:00
PHST- 2009/08/22 09:00 [entrez]
PHST- 2009/08/22 09:00 [pubmed]
PHST- 2009/09/18 06:00 [medline]
PHST- 2010/08/27 00:00 [pmc-release]
AID - 00007890-200908270-00014 [pii]
AID - 10.1097/TP.0b013e3181b0f92f [doi]
PST - ppublish
SO  - Transplantation. 2009 Aug 27;88(4):533-41. doi: 10.1097/TP.0b013e3181b0f92f.