Evidence for a genetic predisposition towards acute rejection after kidney and simultaneous kidney-pancreas transplantation

Transplantation. 2000 Aug 27;70(4):674-80. doi: 10.1097/00007890-200008270-00023.

Abstract

Background: In vitro production of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and transforming growth factor-beta (TGF-beta) correlate with their respective genetic polymorphisms. We analyzed the relationship between these genetic polymorphisms and posttransplant outcome.

Methods: Using DNA polymerase chain reaction (PCR) technology, polymorphisms for TNF-alpha, IFN-gamma, IL-10, and TGF-beta were determined for 82 kidney (K) and 19 simultaneous kidney-pancreas (SKP) recipients. These results were analyzed with regard to the incidence of acute rejection (AR), and the timing and severity of the first AR episode.

Results: A high TNF-alpha production phenotype correlated with recurrent acute rejection (AR) episodes (P<0.026). Compared with the low TNF-alpha production phenotype, more patients with the high production phenotype had a post-AR serum creatinine >2.0 mg/dl, but this was not statistically significant (64 vs. 35%, P=0.12). There was no relationship between TNF-alpha genotype and the time to first AR episode or incidence of graft loss. IFN-gamma production phenotype showed no correlation with any of these clinical outcome parameters. There was an increase in AR incidence as the IL-10 production phenotype increased (low, intermediate, high), but only in low TNF-alpha producer phenotypes (P=0.023).

Conclusions: Patients with a polymorphic cytokine genotype putatively encoding for high in vivo TNF-alpha production, and to a lesser extent IL-10 cytokine genotypes putatively encoding for higher levels of in vivo IL-10 production, had a worse clinical outcome regarding AR episodes. These data support the hypothesis that the strength of alloimmune responsiveness after transplantation in part is genetically determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Cytokines / genetics*
  • Drug Therapy, Combination
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Graft Rejection / epidemiology
  • Graft Rejection / genetics*
  • Haplotypes
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Pancreas Transplantation / immunology*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Retrospective Studies
  • Transforming Growth Factor beta / genetics
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma