Relevance of Toll-like receptor-4 polymorphisms in renal transplantation
Relevance of Toll-like receptor-4 polymorphisms in renal transplantation
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DOI：
10.1111/j.1523-1755.2005.00354.x
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发表时间：
2005-06-01
影响因子：
19.6
通讯作者：
Tiberghien, P
中科院分区：
文献类型：
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作者：
Ducloux, D;Deschamps, M;Tiberghien, P
背景Toll样受体-4（TLR4）的多态性已被报道与对微生物病原体的免疫反应减弱以及普通人群中动脉粥样硬化风险降低相关。我们评估了两种TLR4变异对肾移植受者（RTR）严重感染风险、急性排斥反应发生率和动脉粥样硬化并发症发生率的影响。在238例RTR队列中评估TLR-4多态性。移植后动脉粥样硬化事件、急性排斥反应、严重细菌感染、巨细胞病毒（CMV）疾病和机会性感染作为结局进行评价。移植后平均随访95 - 29个月。27例（11.3%）RTR中存在TLR4基因多态性。具有TLR4多态性的受试者发生移植后动脉粥样硬化事件的可能性较小（RR 0.44 95% CI 0.2t至0.93 P = 0.02）和急性排斥反应（RR 0.41，95% CI 0.30至0.83：P = 0.01），但出现严重细菌感染（RR 1.33; 95% CI 1.12至1.67：P = 0.01）和机会性感染（RR 3.03，95% CI 1.72至8.29，P = 0.008）更频繁。TLR4基因多态性与CMV病的发生有一定的相关性（RR 1.47：95%CI 0.95~2.64; P = 0.08）。具有TLR4多态性的RTR表现出较低的移植后动脉粥样硬化事件和急性同种异体移植排斥反应的风险，但更频繁地经历严重的感染事件。RTR的这一亚组可能受益于较低效力的免疫抑制方案，沿着增加的针对感染因子的预防措施。
Background. Polymorphisms in Toll-like receptor-4 (TLR4) have been reported to be associated with a blunted immune response to microbial pathogens, as well as a decreased risk of atherosclerosis in the general population. We assessed the impact of the two TLR4 variants on the risk of severe infection, the incidence of acute rejection, and the occurrence of atherosclerotic complications in renal transplant recipients (RTR).Methods. TLR-4 polymorphisms were assessed in a cohort of 238 RTR. Post-transplant atherosclerotic events, acute rejection, severe bacterial infection, cytomegalovirus (CMV) disease, and opportunistic infections were evaluated as outcomes.Results. The patients were followed for a mean duration of 95 29 months after transplant. TLR4 polymorphism was observed in 27 (11.3%) RTR. Subjects with TLR4 polymorphisms were less likely to experience post-transplant atherosclerotic events (RR 0.44 95% CI 0.2t to 0.93 P = 0.02) and acute rejection (RR 0.41, 95 % Cl 0.30 to 0.83: P = 0.01), but presented severe bacterial infections (RR 1.33; 95% CI 1.12 to 1.67: P = 0.01) and opportunistic infections (RR 3.03, 95% Cl 1.72 to 8.29, P = 0.008) more frequently. TLR4 polymorphism was marginally associated with CMV disease (RR 1.47:95% Cl 0.95 to 2.64; P = 0.08).Conclusion. RTR with TLR4 polymorphism present a lower risk of post-transplant atherosclerotic events and acute allograft rejection, but experience severe infectious episodes more frequently. This subset of RTR may benefit from a less potent immunosuppression regimen, along with increased preventive measures against infectious agents.