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CC chemokine receptor 5 and renal-transplant survival

M Fischereder1, B Luckow, B Hocher

  • 1Medizinische Poliklinik, Klinikum der Universität München, Pettenkoferstrasse 8a, D-80336, München, Germany.

Lancet (London, England)
|June 14, 2001
PubMed
Abstract

Insights

Individuals with the CCR5-Delta 32 genetic mutation show significantly improved renal transplant survival rates. This CCR5 genetic variation offers a promising avenue for preventing transplant rejection and improving patient outcomes.

Area of Science:

  • Immunogenetics
  • Transplantation immunology
  • Pharmacogenomics

Background:

  • The CC chemokine receptor 5 (CCR5) plays a role in transplant rejection, with a specific deletion (CCR5Delta32) leading to an inactive receptor.
  • CCR5 ligands are upregulated during transplant rejection, attracting CCR5-positive cells to the graft.
  • The CCR5Delta32 allele is present in approximately 1% of white populations.

Purpose of the Study:

  • To investigate the impact of the CCR5Delta32 gene deletion on the survival of renal transplants.
  • To determine if CCR5Delta32 influences the rate of transplant rejection or graft loss.

Main Methods:

  • Genomic DNA from 1227 renal transplant recipients was analyzed for the CCR5Delta32 mutation using PCR.
  • Clinical and demographic data were collected, with complete follow-up for 576 first-time recipients.
  • Graft survival was analyzed using Fisher's exact test and Kaplan-Meier plots with log-rank testing.

Main Results:

  • 21 patients (1.7%) were homozygous for CCR5Delta32.
  • Graft survival was significantly longer in patients homozygous for CCR5Delta32 compared to controls (log-rank p=0.033).
  • The hazard ratio for graft loss was 0.367 (95% CI 0.157-0.859) in the CCR5Delta32 homozygous group.

Conclusions:

  • Homozygosity for CCR5Delta32 is associated with enhanced renal transplant survival.
  • These findings suggest a critical pathophysiological role for CCR5 in transplant loss.
  • Targeting CCR5 may represent a novel strategy for preventing renal transplant failure.

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