Background: About 1% of white populations are homozygous carriers of an allele of the gene for the CC chemokine receptor 5 (CCR5) with a 32 bp deletion (CCR5Delta32), which leads to an inactive receptor. During acute and chronic transplant rejection, ligands for CCR5 are upregulated, and the graft is infiltrated by CCR5-positive mononuclear cells. We therefore investigated the influence of CCR5Delta32 on renal-transplant survival.
Methods: Genomic DNA from peripheral-blood leucocytes of 1227 renal-transplant recipients was screened by PCR for the presence of CCR5Delta32. Demographic and clinical data were extracted from hospital records. Complete follow-up data were available for 576 recipients of first renal transplants. Graft survival was analysed by Fisher's exact test and Kaplan-Meier plots compared with a log-rank test.
Findings: PCR identified 21 patients homozygous for CCR5Delta32 (frequency 1.7%). One patient died with a functioning graft. Only one of the remaining patients lost transplant function during follow-up (median 7.2 years) compared with 78 of the 555 patients with a homozygous wild-type or heterozygous CCR5Delta32 genotype. Graft survival was significantly longer in the homozygous CCR5Delta32 group than in the control group (log-rank p=0.033; hazard ratio 0.367 [95% CI 0.157-0.859]).
Interpretation: Patients homozygous for CCR5Delta32 show longer survival of renal transplants than those with other genotypes, suggesting a pathophysiological role for CCR5 in transplant loss. This receptor may be a useful target for the prevention of transplant loss.