CC chemokine receptor 5 and renal-transplant survival.
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.


RESULTS
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]).


CONCLUSIONS
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.
Fischereder
M
M
Medizinische Poliklinik, Klinikum der Universität München, Pettenkoferstrasse 8a, D-80336, München, Germany.
Luckow
B
B
Hocher
B
B
Wüthrich
R P
RP
Rothenpieler
U
U
Schneeberger
H
H
Panzer
U
U
Stahl
R A
RA
Hauser
I A
IA
Budde
K
K
Neumayer
H
H
Krämer
B K
BK
Land
W
W
Schlöndorff
D
D
D000328:Adult; D000368:Aged; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics*
D019713:Receptors, CCR5