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Presenter: Miguel, Hueso, Barcelona, Spain
Authors: Miguel Hueso, Estanis Navarro, Immaculada Herrero-Fresneda, Inés Rama, Josep Maria Cruzado, Oriol Bestard, Joan Torras, Josep Grinyó
SCR+IF/TA in renal protocol biopsies is associated with a poor graft survival. There is a great interest to determine the molecular mechanisms of SCR+IF/TA with the aim to identify new biomarkers and therapeutic targets. Our group has reported a splicing alteration in the Emk1/hPar1b protein kinase mRNA expression, a regulator of immune system homeostasis, associated with SCR+IF/TA. The goal of this study has been the validation of our previous transcriptomic results, from renal grafts with SCR+IF/TA, in an experimental animal model.
Methods: Microarray analysis identified 33 genes that could be involved in SCR+IF/TA onset. These results have been validated by real time PCR in a second population of 31 renal protocol biopsies from patients in a Csa based immunosuppressant therapy. Overexpressed genes will be validated in an experimental model of IF/TA by real time PCR and inmunohistochemistry. Emk1/hPar1b variants were analysed by PCR.
Results: EMK1/B[+]C[+] variant was detected in 10 grafts, EMK/B[+]C[-] in 15 grafts, EMK1/B[-]C[-] in 6 grafts. EMK1/B[+]C[+] variant is a marker of SCR+IF/TA and is associated with the downregulation of CHD4 (p=0.024), COBLL1 (p<0.0001), SF2/hnRNP-F (p=0.02), MINK1 (p=0.02), and with upregulation of TRAM-like protein (p=0.012), APEX2 (p=0.003), ERN1 (p=0.001), TBCE (p=0.009), RCAN3 (p=0.001), PPP4R2 (p=0.03), and ZNF3 (P=0.047) than Emk1 B[-]C[-] grafts. At this moment we are validating these potential markers in an experimental model of IF/TA.
Summary: There is a genetic landscape associated with the EMK/B[+]C[+] or EMK1/B[-]C[-] variants of EMK1/hPar1b. This genetic landscape could be related to the pathogenics of acute and chronic lesions in renal grafts.
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