A comprehensive genotype–phenotype interaction of different Toll-like receptor variations in a renal transplant cohort

Abstract

To date, the impact of the TLR (Toll-like receptor) system on early and late kidney transplantation outcome, such as ARE (acute rejection episodes) or cardiovascular morbidity and mortality, has still not been elucidated conclusively. Genetically determined alterations in TLR expression exhibit a possibility to evaluate their role in transplantation. In the present study, we sought to determine a comprehensive genotype-phenotype association with early and late allograft outcomes. We studied 11 SNPs (single nucleotide polymorphisms) in TLR2, TLR3, TLR4, TLR5, TLR9 and within a co-molecule CD14 in 265 patients receiving their first kidney transplant and the association of these with the occurrence of DGF (delayed graft function), ARE or MACE (major adverse cardiovascular events). ARE were significantly more frequent in patients carrying the TLR3 TT/CT allele (43.8 compared with 25.8%; P=0.001) as were rates of DGF (21.4 compared with 12.0%; P=0.030). Furthermore, TLR9 was significantly involved in the occurrence of MACE (TLR9 -1237; P=0.030). Interestingly, there was no significant effect of any TLR polymorphism on graft survival or renal function and the incidence of any infection, including CMV (cytomegalovirus) infection. In conclusion, our present study in renal transplant recipients suggests that the TLR system may be involved in both acute rejection and MACE. Modulation of the TLR system may be a promising target in future therapeutic strategies.

Podocytes Are Nonhematopoietic Professional Antigen-Presenting Cells

“…22 There are increasing data supporting a role of TLRs in inflammatory kidney diseases. 17,23,24 Endocytosed antigens usually enter the MHC class II pathway to permit CD4+ T cell activation. Only professional APCs are able to also pass Figure 3.…”

Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children

“…The SNPs at rs3775291 and rs13126816 in the TLR3 gene were correlated with a reduced incidence of genital HSV-2 infection but did not affect disease severity in the infected hosts [35]. The L412F SNP was not associated with HCMV infection in renal transplant recipients, although it was linked with the incidence of acute rejection and graft function [21]. This polymorphism was also over-represented in other diseases, including liver recipients infected with human hepatitis C virus [46], infants with bronchiolitis [47], and individuals with asthma [40] or Japanese encephalitis [48].…”

Clinical significance of the single nucleotide polymorphism TLR2 R753Q in heart transplant recipients at risk for cytomegalovirus disease

“…Two studies on the relevance of the TLR2 R753Q polymorphism in a total of >800 liver transplant recipients found a significantly increased risk for severe CMV disease in patients with a mutated genotype [9,10]. Another study evaluated the polymorphism in 265 kidney-transplant patients and found no significant effect in relation to graft survival, renal function, or incidence of opportunistic infections, including CMV infection [11]. We were unable to identify a significant effect of the polymorphism on incidence of tissueinvasive CMV disease or viremia in 175 HTX patients.…”

“…In contrast, the TLR R753Q polymorphism was not associated with an increased risk for CMV replication and disease in kidney transplant recipients [11]. Moreover, Jablonska et al observed a significantly lower frequency of heterozygosity for the TLR2 R753Q polymorphism in immunocompetent patients with primary CMV infection when compared to non-infected individuals [12].…”