title: Toll-like receptor 4 and CD14 gene polymorphisms in Tunisian kidney transplantation.
abstract: BACKGROUND
  Acute and chronic rejections remain an important cause of graft loss after renal transplantation. Currently, activation of innate immune responses through Toll-like receptors (TLRs) is suspected to be implied in the loss of the transplant tolerance.
  
  
  OBJECTIVE
  We investigated functional single nucleotide polymorphisms (SNPs) of TLR4 and its coreceptor CD14 in kidney transplantation and looked for any potential role in acute rejection (AR) and chronic allograft nephropathy (CAN) and impact on graft survival.
  
  
  METHODS
  TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 209 kidney transplant recipients (KTRs) including 132 treated with mycophenolate mofetil (MMF+). AR occurred in 59 patients and 24 were identified as having CAN by biopsy and scored according to the Banff criteria.
  
  
  RESULTS
  There were no significant associations between TLR4 and CD14 genotypes and alleles and the occurrence of both AR episodes and CAN. Moreover, TLR4 and CD14 SNPs did not seem to influence kidney graft survival. Analysis according to human leukocyte antigen (HLA) compatibility status, positivity of anti-HLA antibodies, and immunosuppression by MMF confirmed the absence of correlation of the investigated SNPs with the graft outcome. In addition, incidence of post-transplantation infections, including cytomegalovirus (CMV) infections, was not influenced by both TLR4 and CD14 SNPs.
  
  
  CONCLUSIONS
  These results suggest that TLR4 (Asp299Gly) and CD14 (C/T -159) functional SNPs do not play a major role in AR, CAN, and kidney graft survival. Therefore, intragraft monitoring of TLR4/CD14 genes expression by messenger RNA (mRNA) would provide clarity on the exact role of these receptors in graft injuries.
authors: Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01), University Tunis El Manar, Charles Nicolle Hospital, Tunis, Tunisia.
authors: H
authors: H
authors: Krichen
authors: Y
authors: Y
authors: Gorgi
authors: T
authors: T
authors: Dhaouadi
authors: Y
authors: Y
authors: Mecheri
authors: I
authors: I
authors: Sfar
authors: R
authors: R
authors: Bardi
authors: M M
authors: MM
authors: Bacha
authors: E
authors: E
authors: Abderrahim
authors: S
authors: S
authors: Jendoubi-Ayed
authors: K
authors: K
authors: Ayed
authors: T
authors: T
authors: Ben Abdallah
mesh_terms: D000208:Acute Disease; D000328:Adult; D000906:Antibodies / Q000097:blood; D002908:Chronic Disease; D003141:Communicable Diseases / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology; D006085:Graft Survival / Q000235:genetics; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D016896:Treatment Outcome; D014416:Tunisia; D055815:Young Adult
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4