Genomics of BKV Viremia and Nephropathy Demonstrate an Upregulated Immune Response, T-Cell Activation, and Natural Killer Cell Activation in Renal Transplant Recipients
Einstein/Montefiore Transplant Program, Albert Einstein College of Medicine, Bronx, NY
Meeting: 2013 American Transplant Congress
Abstract number: 272
Background: The gene expression profiles of transplant patients with BK viremia (BKV) and nephropathy (BKVN) is not well understood. We aimed to investigate the genomics of BKV and BKVN in blood and biopsy samples from our transplant population.
Methods: Clinical information on all patients >18 years of age transplanted between January 1, 2009 to December 31, 2011 was collected (n=289). Patients were monitored for BKV viremia (blood viral PCR>1000) monthly for 6 months, then at 9 and 12 months after transplant. Patients in our “Immune Monitoring Study” who had blood PAXGene samples taken at post-transplant visits and had clinically indicated biopsy samples were used for analysis. The gene expression profiles of the kidney biopsy specimens (3 with BKVN and 12 pre-implantation living-donor) and the blood samples of 3 groups (14 stable post-transplant without BKV viremia or rejection, 19 with BKV viremia and 13 acute/chronic antibody-mediated rejection) were studied by Affymetrix HuGene 1.0 ST expression arrays.
Results: BKV was found in 61 patients (21%) and 4 patients (1.4%) developed BKVN. Compared to normal biopsies, the number of differentially expressed genes using Affymetrix microarrays was 4954 (FDR p<0.01). Gene ontology revealed significant up-regulation of genes implicated in immune response and signaling pathways; including T-cell, B cell, and interferon-gamma activation as well as T cell signaling, co-stimulation and proliferation. Pathogenesis based transcripts revealed significantly increased expression of Interferon-Gamma and Rejection Induced (GRIT), Quantitative Cytotoxic T-cell (QCAT), Quantitative Constitutive Macrophage (CMAT), B-cell (BAT), Natural Killer Cell (NKAT), and Endothelial Cell associated transcripts (ENDAT) indicating an inflammatory immune response. Compared to stable post-transplant patients without BKV viremia or rejection, whole blood gene expression analysis again revealed increased expression of pathogenesis based transcripts of GRIT, QCAT and NKAT in patients with BKV viremia and in patients with acute/chronic antibody-mediated rejection.
Conclusion: Genomic analysis of BKV and BKVN revealed up-regulation of the immune system response; including activation and stimulation of T-cells, natural killer cells and interferon-gamma. These profiles were indistinguishable from those observed in rejection samples.
To cite this abstract in AMA style:
Lubetzky M, Bao Y, Aljanabi A, Marfo K, Ajaimy M, DeBoccardo G, Ye B, Akalin E. Genomics of BKV Viremia and Nephropathy Demonstrate an Upregulated Immune Response, T-Cell Activation, and Natural Killer Cell Activation in Renal Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/genomics-of-bkv-viremia-and-nephropathy-demonstrate-an-upregulated-immune-response-t-cell-activation-and-natural-killer-cell-activation-in-renal-transplant-recipients/. Accessed November 22, 2024.« Back to 2013 American Transplant Congress