CC chemokine receptor 5 and renal-transplant survival
CC chemokine receptor 5 and renal-transplant survival
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DOI：
10.1016/s0140-6736(00)04898-4
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发表时间：
2001-06-02
期刊：
影响因子：
168.9
通讯作者：
Schlöndorff, D
中科院分区：
文献类型：
--
作者：
Fischereder, M;Luckow, B;Schlöndorff, D
大约1%的白色人群是CC趋化因子受体5（CCR 5）基因等位基因的纯合携带者，该等位基因具有32 bp缺失（CCR 5 Delta 32），导致受体失活。在急性和慢性移植排斥反应期间，CCR 5的配体上调，移植物被CCR 5阳性单核细胞浸润。因此，我们研究了CCR 5 Delta 32对肾移植存活率的影响。方法采用PCR方法对1227例肾移植受者外周血白细胞基因组DNA进行CCR 5 Delta 32的筛查。人口统计学和临床数据从医院记录中提取。完整的随访数据可用于576例首次肾移植受者。移植物存活率进行了分析，Fisher精确检验和Kaplan-Meier图与log-rank test.Findings PCR确定了21例CCR 5 δ 32纯合子（频率1.7%）。1例患者在移植物功能正常时死亡。在随访期间（中位数7.2年），只有1例患者失去了移植功能，而555例纯合野生型或杂合CCR 5 Delta 32基因型患者中有78例失去了移植功能。移植物存活率在纯合子CCR 5 Δ 32组中显著长于对照组（对数秩p=0.033;危害比0.367 [95%CI 0.157-0.859]）。解释CCR 5 Δ 32纯合子患者显示肾移植物存活率长于具有其它基因型的患者，表明CCR 5在移植物丢失中的病理生理作用。该受体可能是预防移植物丢失的有用靶点。
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 (CCR5 Delta 32), 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 CCR5 Delta 32 on renal-transplant survivalMethods Genomic DNA from peripheral-blood leucocytes of 1227 renal-transplant recipients was screened by PCR for the presence of CCR5 Delta 32. 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 CCR5 Delta 32 (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 CCR5 Delta 32 genotype. Graft survival was significantly longer in the homozygous CCR5 Delta 32 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 CCR5 Delta 32; 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.