C-C趋化因子受体5与肾移植存活

CC chemokine receptor 5 and renal-transplant survival.

作者信息

Fischereder M, Luckow B, Hocher B, Wüthrich R P, Rothenpieler U, Schneeberger H, Panzer U, Stahl R A, Hauser I A, Budde K, Neumayer H, Krämer B K, Land W, Schlöndorff D

机构信息

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

出版信息

Lancet. 2001 Jun 2;357(9270):1758-61. doi: 10.1016/s0140-6736(00)04898-4.

DOI:10.1016/s0140-6736(00)04898-4

PMID:11403814

Abstract

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.

摘要

背景

约1%的白种人群是CC趋化因子受体5（CCR5）基因一个等位基因的纯合携带者，该等位基因存在32bp的缺失（CCR5Delta32），会导致受体失活。在急性和慢性移植排斥反应期间，CCR5的配体上调，且移植器官被CCR5阳性单核细胞浸润。因此，我们研究了CCR5Delta32对肾移植存活的影响。

方法

采用聚合酶链反应（PCR）对1227例肾移植受者外周血白细胞的基因组DNA进行筛查，以检测CCR5Delta32的存在情况。从医院记录中提取人口统计学和临床数据。576例首次肾移植受者有完整的随访数据。采用Fisher精确检验分析移植肾存活情况，并用对数秩检验比较Kaplan-Meier曲线。

结果

PCR鉴定出21例CCR5Delta32纯合患者（频率为1.7%）。1例患者移植肾仍有功能时死亡。在随访期间（中位时间7.2年），其余患者中只有1例移植肾功能丧失，而555例纯合野生型或CCR5Delta32杂合基因型患者中有78例出现移植肾功能丧失。CCR5Delta32纯合组的移植肾存活时间明显长于对照组（对数秩检验p=0.033；风险比0.367[95%可信区间0.157-0.859]）。