Peripheral blood gene expression analysis in intestinal transplantation: a feasibility study for detecting novel candidate biomarkers of graft rejection.

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.

Body surface area index predicts outcome in orthotopic liver transplantation.

BACKGROUND/PURPOSE: In living donor liver transplantation (LDLT), matching of liver volume between donor and recipient is critical to the success of the procedure; mismatch can result in 'small- or large-for-size syndrome'. In orthotopic liver transplantation (OLT), matching criteria are less stringent and non-uniform. We sought to determine whether a new parameter, the ratio of donor to recipient body surface area (BSAi), is predictive of size mismatch and/or post-transplant morbidity or mortality. METHODS: We reviewed data on 1228 OLT recipients and stratified this data according to three categories: small-for-size (BSAi <0.6), control (BSAi = 0.6-1.4), and large-for-size (BSAi >1.4) donors. RESULTS: We found that: (1) matching of grafts at the upper and lower extremes of BSAi had significantly reduced graft survival; (2) matches with lower BSAi sustained a less severe form of intraoperative post-reperfusion syndrome, and the incidence of hepatic artery thrombosis was high postoperatively in these grafts; (3) BSAi and donor age correlated well with the severity of intraoperative post-reperfusion hypotension; and (4) small-for-size (BSAi <0.6) and large-for-size (BSAi >1.4) grafts, as well as preoperative total bilirubin, were significant risk factors for decreased graft survival. CONCLUSION: We conclude that the BSAi can predict clinically significant size mismatch and adverse outcomes in cadaveric whole OLT.