title: Peripheral blood gene expression analysis in intestinal transplantation: a feasibility study for detecting novel candidate biomarkers of graft rejection.
abstract: BACKGROUND
  We investigated the putative candidate biomarkers of graft rejection in peripheral blood of intestinal transplant patients.
  
  
  METHODS
  Peripheral blood gene expression analysis was performed in intestinal transplant patients. The results were matched with concurrent graft biopsies using bioinformatics.
  
  
  RESULTS
  Peripheral blood samples (n=11), of 3 adult patients [transplant day (n=1), no rejection (n=1), minimal rejection (n=2), mild rejection (n=5) and severe rejection (n=2)] were collected. Bioinformatics: Enrichment Analysis: The three most affected pathways differentially expressed in rejection versus a pool of healthy volunteers were related to protein translation: translation initiation, translation elongation termination, and translation in mitochondria, with p-values for all rejection stages in all patients in the 10-4 to 10-18 range. No significant enrichment was observed for these categories in the day of transplant sample. In addition to translation, significant enrichment of several immune response categories was observed in rejection samples. Subsequent gene set enrichment analysis verified these results. The level of enrichment was very high (p-values of 10-5-10-60) and increased with the level of rejection in all patients. Genes significantly down-regulated in translation related gene sets included ribosomal proteins RPL13A, RP L22, RPS23, RPL13 and RPL10A, that could be used as potential biomarkers for future experiments.
  
  
  CONCLUSIONS
  In this pilot study we found a list of genes (involved in translation) significantly downregulated in the peripheral blood of three intestinal transplant patients during rejection. These results will be verified in further studies with increased number of patients and with isolation of peripheral blood subpopulations.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, FL, USA.
authors.forename: Victor P
authors.initials: VP
authors.lastname: Andreev
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tryphonopoulos
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Blomberg
authors.forename: Nick
authors.initials: N
authors.lastname: Tsinoremas
authors.forename: Debbie
authors.initials: D
authors.lastname: Weppler
authors.forename: Danielle-Rachel
authors.initials: DR
authors.lastname: Neuman
authors.forename: Alex
authors.initials: A
authors.lastname: Volsky
authors.forename: Seigo
authors.initials: S
authors.lastname: Nishida
authors.forename: Akin
authors.initials: A
authors.lastname: Tekin
authors.forename: Gennaro
authors.initials: G
authors.lastname: Selvaggi
authors.forename: David M
authors.initials: DM
authors.lastname: Levi
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakis
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D001773:Blood Cells / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D006084:Graft Rejection / Q000097:blood / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D010443:Peptide Chain Termination, Translational / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics
chemical_list: D015415:Biomarkers; D012269:Ribosomal Proteins