Peripheral blood gene expression analysis in intestinal transplantation

A feasibility study for detecting novel candidate biomarkers of graft rejection

Victor P. Andreev, Panagiotis Tryphonopoulos, Bonnie B Blomberg, Nicholas Tsinoremas, Debbie Weppler, Danielle Rachel Neuman, Alex Volsky, Seigo Nishida, Akin Tekin, Gennaro Selvaggi, David M. Levi, Andreas G. Tzakis, Phillip Ruiz

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1385-1394
Number of pages10
JournalTransplantation
Volume92
Issue number12
DOIs
StatePublished - Dec 27 2011

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Graft Rejection
Feasibility Studies
Transplantation
Biomarkers
Transplants
Gene Expression
Computational Biology
Genes
Patient Isolation
Ribosomal Proteins
Protein Biosynthesis
Healthy Volunteers
Mitochondria
Down-Regulation
Biopsy

Keywords

  • Gene expression
  • Intestinal transplantation
  • Rejection

ASJC Scopus subject areas

  • Transplantation

Cite this

Peripheral blood gene expression analysis in intestinal transplantation : A feasibility study for detecting novel candidate biomarkers of graft rejection. / Andreev, Victor P.; Tryphonopoulos, Panagiotis; Blomberg, Bonnie B; Tsinoremas, Nicholas; Weppler, Debbie; Neuman, Danielle Rachel; Volsky, Alex; Nishida, Seigo; Tekin, Akin; Selvaggi, Gennaro; Levi, David M.; Tzakis, Andreas G.; Ruiz, Phillip.

In: Transplantation, Vol. 92, No. 12, 27.12.2011, p. 1385-1394.

Research output: Contribution to journalArticle

Andreev, Victor P. ; Tryphonopoulos, Panagiotis ; Blomberg, Bonnie B ; Tsinoremas, Nicholas ; Weppler, Debbie ; Neuman, Danielle Rachel ; Volsky, Alex ; Nishida, Seigo ; Tekin, Akin ; Selvaggi, Gennaro ; Levi, David M. ; Tzakis, Andreas G. ; Ruiz, Phillip. / Peripheral blood gene expression analysis in intestinal transplantation : A feasibility study for detecting novel candidate biomarkers of graft rejection. In: Transplantation. 2011 ; Vol. 92, No. 12. pp. 1385-1394.
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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.",
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T1 - Peripheral blood gene expression analysis in intestinal transplantation

T2 - A feasibility study for detecting novel candidate biomarkers of graft rejection

AU - Andreev, Victor P.

AU - Tryphonopoulos, Panagiotis

AU - Blomberg, Bonnie B

AU - Tsinoremas, Nicholas

AU - Weppler, Debbie

AU - Neuman, Danielle Rachel

AU - Volsky, Alex

AU - Nishida, Seigo

AU - Tekin, Akin

AU - Selvaggi, Gennaro

AU - Levi, David M.

AU - Tzakis, Andreas G.

AU - Ruiz, Phillip

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N2 - 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.

AB - 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.

KW - Gene expression

KW - Intestinal transplantation

KW - Rejection

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