Relevance of Toll-like receptor-4 polymorphisms in renal transplantation

被引:130
作者
Ducloux, D [1 ]
Deschamps, M
Yannaraki, M
Ferrand, C
Bamoulid, J
Saas, P
Kazory, A
Chalopin, JM
Tiberghien, P
机构
[1] CHU Saint Jacques, Dept Nephrol Dialysis & Renal Transplantat, Besancon, France
[2] Etab Francais Sang Bourgogne Franche Comte, Besancon, France
[3] INSERM, U645, EA 2284 IFR 133, Besancon, France
关键词
TLR4; polymorphism; renal transplantation; acute rejection; cardiovascular disease; infection;
D O I
10.1111/j.1523-1755.2005.00354.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:2454 / 2461
页数:8
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