title: The effect of low and ultra-low dosages Thymoglobulin on peripheral T, B and NK cells in kidney transplant recipients.
abstract: BACKGROUND
  Rabbit Anti-Thymocyte Globulin (r-ATG) is a polyclonal antibody preparation, used to prevent and treat acute rejection episodes after organ transplantation. However, despite more than 40 years of clinical use, the optimal dose of r-ATG is still not defined. To find a better balance between efficacy and infectious complications, we embarked on a controlled study and monitored the effect of low and ultra-low dosages Thymoglobulin (Genzyme) on peripheral T, B, and NK cells.
  
  
  METHODS
  Kidney transplant recipients received either 0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg on the first 3 consecutive days post-transplantation. Thus, total doses were 1.5 mg/kg, 3.0 mg/kg and 6.0 mg/kg. A total of 40 patients were enrolled, including 11 controls. All patients were treated with Prednisolon, Advagraf (Astellas) and Mycophenolate Mofetil (Roche). T (CD3+), B (CD19+) and NK (CD3-CD16+56+) cells were analyzed by flow cytometry. Baseline cell counts were compared to forty age and sex matched healthy persons. Post-transplantation cell counts of the 3 Thymoglobulin groups were compared to the 11 control patients, who received no induction therapy.
  
  
  RESULTS
  Absolute numbers of T, B, and NK cells were comparable in all patients pre-transplantation, but T and B cells were lower than in healthy persons (p=0.007 and p=0.0003, Mann Whitney test). In the first week, T cells and NK cells were significantly lower in all Thymoglobulin groups compared to controls. B cells were not affected. One month after Thymoglobulin NK cells had returned to control numbers in all groups, while T cells had already recovered to control counts in the 1.5 mg/kg group. During follow-up, T cells in the 3.0mg/kg group also returned to control values, but at one year the patients in the 6.0 mg/kg group still had significantly lower T cells (p=0.03). Patient and graft survival, rejection and infection incidence and renal function did not differ between groups.
  
  
  CONCLUSIONS
  Patients with end stage renal disease have significantly lower peripheral T and B cell counts than healthy persons. (Ultra-) low Thymoglobulin schedules deplete peripheral lymphocytes in a dose dependent way. Knowledge of the duration of this depletion contributes to finding the optimal immunosuppressive strategy for kidney transplant recipients.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands. m.kho@erasmusmc.nl
authors.forename: M M L
authors.initials: MM
authors.lastname: Kho
authors.forename: A P
authors.initials: AP
authors.lastname: Bouvy
authors.forename: M
authors.initials: M
authors.lastname: Cadogan
authors.forename: R
authors.initials: R
authors.lastname: Kraaijeveld
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D054796:Drug Dosage Calculations; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy; D007676:Kidney Failure, Chronic / Q000628:therapy*; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; C512542:thymoglobulin