title: Successful reduction of immunosuppression in older renal transplant recipients who exhibit donor-specific regulation.
abstract: 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 Twenty-two patients had prednisone withdrawn during a 3-month period, whereas 10 controls were maintained on triple therapy (prednisone, cyclosporine, and mycophenolate).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.affiliation: Department of Surgery, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jankowska-Gan
authors.forename: Hans W
authors.initials: HW
authors.lastname: Sollinger
authors.forename: John D
authors.initials: JD
authors.lastname: Pirsch
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Haynes
authors.forename: Alenjandro
authors.initials: A
authors.lastname: Munoz del Rio
authors.forename: William J
authors.initials: WJ
authors.lastname: Burlingham
mesh_terms: D000208:Acute Disease; D000368:Aged; D000375:Aging / Q000276:immunology*; D000818:Animals; D065095:Calcineurin Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D006968:Hypersensitivity, Delayed; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011241:Prednisone / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone
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