Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
TCMR is characterized by the reduction of vessel lumen with marked intimal thickening, fibrous hyperplasia and a strong component of leukocyte infiltrate. Aim of our work has been the study of gene expression profile in renal tissue, including the cellular infiltrate, in TCMR biopsies.
We have performed transcriptomics study using RNA extracted from archival formalin-fixed and paraffin-embedded (FFPE) renal biopsies obtained from 21 patients with TCMR, 10 with T-cell mediated acute rejection (TCAR) and 10 with chronic calcineurin inhibitor toxicity (CNITOX). Controls were renal tissue samples from 52 cadaveric donors (CD). Genome-wide expression profiles were generated by Illumina platform. Real-Time PCR was used for validation of the identified transcripts.
Using a FC≥2 and a FDR<0.05, we identified 139 genes differentially expressed in the renal tissue of patients with TCMR compared to CD. Principal Component Analysis showed a clear difference in the gene expression of the two groups of biopsies. The study of gene pathways showed upregulation of OX40 gene signaling, that is involved in the differentiation of memory effector T cell, and up-regulation of KLRG1, BLIMP1 and IL2RB gene that characterized CD8+ short-lived memory effector T cells. Then, we compared TCMR gene expression profile with TCAR. CNITOX were used as control group to minimize therapy effect on gene modulation. Comparative analysis revealed 117 specific genes for TCMR. Interestingly, we found that OX40 signaling was specific only for TCMR. Moreover, real-time PCR validation for OX40, KLRG1, BLIMP1 and IL2RB confirmed that these genes were up-regulated in TCMR but not in TCAR.
Our data show, for the first time, a cluster of genes, mainly OX40, that suggest the involvement of memory committed CD8+ effector T cells in TCMR. They are short-lived terminally differentiated CD8+ T-regs that exhibit highly suppressive, proliferative and apoptotic activity in non-lymphoid tissue. The identified genes may be used as a target for specific treatment of TCMR.
To cite this abstract in AMA style:Schena F, Curci C, Sallustio F, Trpevski M, Palma GDe, Fiorentino M, Rossini M, Quaglia M, Bozzola E, Zanini S, Furian L, Toscano A, Gallo E, Gesualdo L, Stratta P, Rigotti P, Citterio F, Biancone L. OX40 Gene: A Potential Target for the Care of Chronic T-Cell Mediated Rejection (TCMR) [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/ox40-gene-a-potential-target-for-the-care-of-chronic-t-cell-mediated-rejection-tcmr/. Accessed September 27, 2021.
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