Relevance of Toll-like receptor-4 polymorphisms in renal transplantation.
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 0.21 to 0.93; P= 0.02) and acute rejection (RR 0.41; 95% CI 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% CI 1.72 to 8.29; P= 0.008) more frequently. TLR4 polymorphism was marginally associated with CMV disease (RR 1.47; 95% CI 0.95 to 2.64; P= 0.08).


CONCLUSIONS
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.
Ducloux
Didier
D
Department of Nephrology, Dialysis, and Renal Transplantation, CHU Saint Jacques, Besançon, France. dducloux@chu-besancon.fr
Deschamps
Marina
M
Yannaraki
Maria
M
Ferrand
Christophe
C
Bamoulid
Jamal
J
Saas
Philippe
P
Kazory
Amir
A
Chalopin
Jean-Marc
JM
Tiberghien
Pierre
P
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology; D003586:Cytomegalovirus Infections / Q000209:etiology; D005260:Female; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors