Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy
Background. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV. We hypothesized that PBMC gene expression prof...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Journal of Transplantation |
| Online Access: | http://dx.doi.org/10.1155/2010/719696 |
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| author | Khurram Shahzad Martin Cadeiras Sarfaraz Memon Barry Zeeberg Tod Klingler Anshu Sinha Esteban G. Tabak Sreevalsa Unniachan Mario C. Deng |
| author_facet | Khurram Shahzad Martin Cadeiras Sarfaraz Memon Barry Zeeberg Tod Klingler Anshu Sinha Esteban G. Tabak Sreevalsa Unniachan Mario C. Deng |
| author_sort | Khurram Shahzad |
| collection | DOAJ |
| description | Background. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV. We hypothesized that PBMC gene expression profiles (GEP) can identify patients at risk of CAV. Methods. We retrospectively analyzed a limited set of whole-genome PBMC microarrays from 10 post-transplant patients who did (n=3) or did not (n=7) develop advanced grade CAV during their long-term follow-up. We used significance analysis of microarrays to identify differentially expressed genes and High-Throughput GoMiner to assess gene ontology (GO) categories. We corroborated our findings by retrospective analysis of PBMC real-time PCR data from 33 patients. Results. Over 300 genes were differentially expressed (FDR < 5%), and 18 GO-categories including “macrophage activation”, “Interleukin-6 pathway”, “NF-KappaB cascade”, and “response to virus” were enriched by these genes (FDR < 5%). Out of 8 transcripts available for RT-PCR analysis, we confirmed 6 transcripts (75.0%) including FPRL1, S100A9, CXCL10, PRO1073, and MMP9 (P<.05). Conclusion. Our pilot data suggest that GEP of PBMC may become a valuable tool in the evaluation of patients at risk of CAV. Larger prospectively designed studies are needed to corroborate our hypothesis. |
| format | Article |
| id | doaj-art-e5c8c53ac94848d39d558e3ba5ae0280 |
| institution | Kabale University |
| issn | 2090-0007 2090-0015 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Transplantation |
| spelling | doaj-art-e5c8c53ac94848d39d558e3ba5ae02802025-02-03T05:47:35ZengWileyJournal of Transplantation2090-00072090-00152010-01-01201010.1155/2010/719696719696Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft VasculopathyKhurram Shahzad0Martin Cadeiras1Sarfaraz Memon2Barry Zeeberg3Tod Klingler4Anshu Sinha5Esteban G. Tabak6Sreevalsa Unniachan7Mario C. Deng8Division of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADivision of Cardiology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADivision of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USAGenomics and Bioinformatics Group, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAXDx Inc., Brisbane, CA 94005, USADivision of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USACourant Institute of Mathematical Science, New York University, New York, NY 10012, USADivision of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADivision of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USABackground. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV. We hypothesized that PBMC gene expression profiles (GEP) can identify patients at risk of CAV. Methods. We retrospectively analyzed a limited set of whole-genome PBMC microarrays from 10 post-transplant patients who did (n=3) or did not (n=7) develop advanced grade CAV during their long-term follow-up. We used significance analysis of microarrays to identify differentially expressed genes and High-Throughput GoMiner to assess gene ontology (GO) categories. We corroborated our findings by retrospective analysis of PBMC real-time PCR data from 33 patients. Results. Over 300 genes were differentially expressed (FDR < 5%), and 18 GO-categories including “macrophage activation”, “Interleukin-6 pathway”, “NF-KappaB cascade”, and “response to virus” were enriched by these genes (FDR < 5%). Out of 8 transcripts available for RT-PCR analysis, we confirmed 6 transcripts (75.0%) including FPRL1, S100A9, CXCL10, PRO1073, and MMP9 (P<.05). Conclusion. Our pilot data suggest that GEP of PBMC may become a valuable tool in the evaluation of patients at risk of CAV. Larger prospectively designed studies are needed to corroborate our hypothesis.http://dx.doi.org/10.1155/2010/719696 |
| spellingShingle | Khurram Shahzad Martin Cadeiras Sarfaraz Memon Barry Zeeberg Tod Klingler Anshu Sinha Esteban G. Tabak Sreevalsa Unniachan Mario C. Deng Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy Journal of Transplantation |
| title | Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy |
| title_full | Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy |
| title_fullStr | Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy |
| title_full_unstemmed | Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy |
| title_short | Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy |
| title_sort | gene expression signatures of peripheral blood mononuclear cells during the early post transplant period in patients developing cardiac allograft vasculopathy |
| url | http://dx.doi.org/10.1155/2010/719696 |
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