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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients
Khurram Shahzad1, Martin Cadeiras, Sarfaraz Memon
1Division of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Insights
Peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) show promise for early detection of cardiac allograft vasculopathy (CAV) after heart transplantation. This GEP approach may help identify patients at risk for CAV, improving graft survival.
Area of Science:
- Immunology
- Genomics
- Transplantation Medicine
Background:
- Cardiac allograft vasculopathy (CAV) is a primary cause of graft failure and mortality post-heart transplantation.
- Current diagnostic methods lack the ability to identify patients at high risk for CAV in the early post-transplant phase.
Purpose of the Study:
- To investigate the potential of peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) for identifying patients at risk of developing CAV.
- To establish early diagnostic markers for CAV risk stratification.
Main Methods:
- Retrospective analysis of whole-genome PBMC microarrays from 10 heart transplant recipients (3 with CAV, 7 without).
- Utilized Significance Analysis of Microarrays and High-Throughput GoMiner for differential gene expression and gene ontology analysis.
- Corroborated findings with PBMC real-time PCR data from 33 patients.
Main Results:
- Over 300 differentially expressed genes (FDR < 5%) were identified.
- Enrichment analysis revealed 18 gene ontology categories, including "macrophage activation" and "Interleukin-6 pathway" (FDR < 5%).
- Six of eight (75%) tested transcripts, including FPRL1, S100A9, CXCL10, PRO1073, and MMP9, were confirmed via RT-PCR (P < .05).
Conclusions:
- PBMC GEP shows potential as a valuable tool for assessing CAV risk in heart transplant patients.
- Further prospective studies are required to validate these preliminary findings and clinical utility.
Abstract:
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.
