Abstract:
INTRODUCTION:We investigated the putative candidate biomarkers of graft rejection in peripheral blood of intestinal transplant patients. MATERIALS AND 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. CONCLUSION: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.
journal_name
Transplantationjournal_title
Transplantationauthors
Andreev VP,Tryphonopoulos P,Blomberg BB,Tsinoremas N,Weppler D,Neuman DR,Volsky A,Nishida S,Tekin A,Selvaggi G,Levi DM,Tzakis AG,Ruiz Pdoi
10.1097/TP.0b013e3182370db1subject
Has Abstractpub_date
2011-12-27 00:00:00pages
1385-91issue
12eissn
0041-1337issn
1534-6080pii
00007890-201112270-00015journal_volume
92pub_type
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