title: Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants.
abstract: BACKGROUND
  Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection.
  
  
  METHODS
  Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure.
  
  
  RESULTS
  Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment.
  
  
  CONCLUSIONS
  Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.
authors.affiliation: Department of Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Alexander
authors.forename: S B
authors.initials: SB
authors.lastname: Younes
authors.forename: J J
authors.initials: JJ
authors.lastname: Yunis
authors.forename: D
authors.initials: D
authors.lastname: Zurakowski
authors.forename: N
authors.initials: N
authors.lastname: Mirza
authors.forename: D
authors.initials: D
authors.lastname: Dubey
authors.forename: M P
authors.initials: MP
authors.lastname: Drew
authors.forename: W E
authors.initials: WE
authors.lastname: Harmon
authors.forename: E J
authors.initials: EJ
authors.lastname: Yunis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006238:Haploidy; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007223:Infant; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome