title: Cardiac allograft rejection correlates with increased expressions of Toll-like receptors 2 and 4 and allograft inflammatory factor 1.
abstract: BACKGROUND
  Evidence suggests that injury-induced activation of the recipient's innate immune response determines the outcome of allograft transplantation. The mechanism responsible for the induction of such innate immune response is not clear yet. We hypothesized that in cardiac transplantation settings, the initial myocardial ischemia and postischemia graft reperfusion may release allograft inflammatory factor (AIF) 1, causing Toll-like receptor (TLR)-mediated activation of macrophages and dendritic cells, leading to the production of cytokines and the activation of adaptive alloimmunity. Therefore, our goal was to validate the presence of these biomarkers in the peripheral blood and biopsy specimens of patients presenting allograft rejection.
  
  
  METHODS
  We studied 90 peripheral blood and 30 endomyocardial biopsy specimens from patients who had undergone cardiac transplantation. Specimens were tested by quantitative reverse-transcription polymerase chain reaction to determine TLR-2 and -4 and AIF-1 expression levels, correlating with clinical rejection grades. The group differences for mRNA transcript levels between the rejection grades were determined by 1-way analysis of variance. The level of significance was set at P < .05 for comparison between the groups.
  
  
  RESULTS
  The mean ± SEM level of TLR-2 mRNA expression was increased 1.7-fold in monocytes (P < .05) and 4.2-fold in biopsy samples from groups with grade 3A compared with grade 1A or grade 0 rejection (P < .0001). AIF-1 expression was increased 2.4-fold in monocytes (P < .05) and 4.2-fold in biopsy samples comparing grade 3A versus 1A rejections. The TLR-4 mRNA expression was also increased in the group with 3A rejections; however, the difference was only significant in biopsy specimens (P < .0001).
  
  
  CONCLUSIONS
  Our data demonstrated that expression profiles of AIF-1 and TLR-2 correlated with biopsy-proven allograft rejection in both peripheral blood and local tissue, suggesting their potential as diagnostic biomarkers for early detection of allograft rejection.
authors.affiliation: Department of Surgery, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA. omcdaniel@umc.edu
authors.forename: D O
authors.initials: DO
authors.lastname: McDaniel
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: C K
authors.initials: CK
authors.lastname: Moore
authors.forename: G
authors.initials: G
authors.lastname: Aru
mesh_terms: D001706:Biopsy; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007113:Immunity, Innate; D008840:Microfilament Proteins; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4