Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: CAMR is the main cause of chronic graft injury and subsequent graft loss. Most of the studies on the subject focused their attention to either B cells and CD4+ T cells dysregulation, whereas very little is known on the potential role of CD8+ T cells in this setting. We have previously demonstrated an increase in infiltrating CD8+ T cells in the glomeruli of CAMR biopsies. The aim of the present study was to investigate the molecular mechanisms underlying the development of CAMR focusing on gene expression profiles of circulating CD8+ T lymphocytes
*Methods: We enrolled 14 patients with biopsy-proven CAMR and 12 stable transplant recipients with normal graft histology and function (control group). Gene expression profiles of CD8+ T lymphocytes isolated from both groups were assessed using Agilent microarrays. Our results were evaluated by statistical analysis (unpaired and moderated t tests with Benjamini-Hochberg correction, Storey q-value computation) and functional pathway analysis (Ingenuity Pathway Analysis) and validated by qPCR in an independent set of patients. To analyze the genome-wide expression of CD8+ T lymphocytes isolated, we enrolled an independent cohort of 4 CAMR patients and 4 control subjects. The remaining patients were employed to validate the microarray data by qPCR.
*Results: Gene expression profiles of CD8+ T cells revealed that triacylglycerol biosynthesis (p=2.69E-3) was the main dysregulated canonical pathway. Among the main diseases and bio-functions pathways, deregulation of the lipid metabolism features the CAMR patients. In this setting we observed a significant change in the genes related to the release of prostaglandins (p=5.3E-5), in particular prostaglandin E2 (p=2.95E-4), and the release of eicosanoids (p=4.41E-4). The main genes involved in these metabolic pathways were CERK (FC=-2.7), HMGB1 (FC=+2.02), LPIN1 (FC=+2.07), NAMPT (FC=+2.39), TNFSF10 (FC=+2.07). All the changes in the expression of these genes in CAMR vs control patients was confirmed by qPCR (p<0.05).
*Conclusions: In conclusion, our data would suggest a significant change in CD8+ activation in CAMR patients mainly characterized by a marked deregulation of lipid-related metabolic pathways. This observation may suggest that metabolic alterations may influence immune response in CAMR as already described for autoimmune diseases.
To cite this abstract in AMA style:Pontrelli P, Rascio F, Accetturo M, Castellano G, Simone S, Stallone G, Gesualdo L, Grandaliano G. Gene Expression Profiles in CD8+ T Cells in Chronic Antibody-Mediated Rejection (CAMR) of Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/gene-expression-profiles-in-cd8-t-cells-in-chronic-antibody-mediated-rejection-camr-of-kidney-transplantation/. Accessed August 1, 2021.
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