Transcriptomic Profile in Pancreas Biopsies for Monitoring Graft Rejection

VENTURA AGUIAR, P; RAMIREZ BAJO MJ; ROUFOSSE C; CUATRECASAS M; ROVIRA J; BAÑON MANEUS E; FONDEVILLA C; CAMPISTOL JM; UVA P; DRACHENBERG, CINTHIA; DIEKMANN FRITZ

San Diego

Congreso; XVIII World Congress of the International Pancreas and Islet Transplant Association; 2021

IPITA

Introduction: Overall, almost 30% of pancreas transplant recipients presentan episode of rejection during the first year after transplantation. Pancreasbiopsy is the gold standard for the diagnosis and treatment pancreas rejectionsince other modes of monitoring pancreas rejection are neither sensitivenor specific enough. Immune infiltrates of graft from transplantationsare usually evaluated with immunohistochemistry, immunofluorescence andflow cytometry. Interestingly enough, Banff schema has refined the diagnosisin kidney antibody-mediated rejection (ABMR) 4 times in the last 10 years,whereas in pancreas transplantation it has remained unchanged since its firstdescription in 2011.Identification of genetic variants to aid in individualized treatment of solidorgan allograft recipients would be associated with outcomes and personalizedmedicine. In kidney, liver, and heart transplantation, the molecularmicroscope has been paving the way towards the introduction of these noveltranscriptomic fingerprints into the clinical practice and provide assistanceinto decision making. In pancreas transplantation only one work exploredthe correlation between the transcriptomic fingerprint and development of denovo ABMR using a 34 gene-set.Methods: We are developing a retrospective multicentre observational studyaiming at comparing the transcriptomic profile of RNA obtained from paraffinembedded pancreas graft biopsies, and compare to the clinical andbiochemical markers, and histological diagnosis. Study is being developedusing pancreas graft biopsies performed previously per protocol or clinicalindication. Samples from a range of different histological diagnosis (accordingto the Banff criteria) will be included (estimated n=20/diagnosis). Briefly, 3sections of 20-micron thickness were obtained from FFPE blocks and RNAextraction were performed with the RNeasy FFPE Kit (Qiagen). Quality andquantity of RNA was checked by NanoDrop ND1000 (Thermo Scientific)spectrophotometer.For transcriptome analysis we are applying the Human Organ Transplantpanel from Nanostring©, which includes a comprehensively profile of 770genes across 37 pathways to identify biomarkers for rejection, uncover themechanisms of tissue damage, and study toxicities brought on by immunosuppressivedrugs.We expect to have preliminary results by May and some more conclusivedata by November 2021.Copyright