Expression of TLR-4 and -2 in peripheral mononuclear cells in renal transplant patients with TLR-4 gene polymorphism

IntroductionTLR-4 has also been identified as a receptor for endogenous alarmins, which are increased post transplantation. TLR-4 has also been associated with a polymorphism that could impact graft outcome.ObjectiveTo assess the expression of TLR-4 in kidney transplant patients carrying or not a polymorphism.MethodsTLR-4 polymorphism (A299G/T399I) was studied in 200 renal transplant patients. Healthy volunteers were also enrolled as control group. The polymorphism analysis was performed using restriction enzymes technique (RFLP). Functionality of TLR-4 polymorphism was assessed in samples from controls by quantification of TNF-α after LPS stimulus. TLR-4 and -2 expressions were also analyzed by flow cytometry.ResultsTLR-4 polymorphism was present in 8.5% of renal transplant patients. This polymorphism was associated with impairment in TNF-α secretion. In general, in renal transplant patients, TLR-4 expression in monocytes and in neutrophils was lower than in health volunteers. TLR-2 and TLR-4 expressions in healthy volunteers with A299G/T399I TLR-4 polymorphism was higher than in wild-type genotype healthy volunteers (p < 0.01 and p < 0.05, respectively), and also higher than A299G/T399I TLR-4 polymorphism renal transplant patients (p < 0.05). TLR-2 expression on neutrophils in wild-type genotype renal transplant patients was higher compared to wild-type genotype healthy volunteers, and was also higher in relation to A299G/T399I kidney transplanted patients (p < 0.01).ConclusionStable renal transplant patients with TLR-4 polymorphism have a lower expression of TLR-4 and TLR-2 receptors in peripheral mononuclear cells, which ultimately indicate a less responsiveness for alarmins.

Research Highlights
► TLR-4 polymorphism showed a lower expression in renal transplant patients.
► TLR-4 polymorphism was associated with impairment in TNF-α secretion.
► TLR-2 showed more expression in mononuclear cells.
► Renal transplant TLR4 polymorphism patients, showed lower serum creatinine in 7 days.