Renal allograft transcription analysis with NanoStringⓇ nCounterⓇ analysis system reveals similar signature of acute T cell mediated rejection in patients treated with tacrolimus or belatacept

M. van der Zwan, C.C. Baan, R.B. Colvin, R.N. Smith, R.A. White, D. Ndishibandi, G.N. de Graav, M.C. Clahsen-van Groningen, D.A. Hesselink

Thursday 15 march 2018

12:50 - 13:00h at Van Weelde Zaal

Categories: Basic / translational research, Session (parallel)

Parallel session: Parallel session 2: Basic / translational research

Introduction

Identification of biomarkers of acute kidney allograft rejection (AR) can potentially lead to improved diagnostics. Here, we analyzed the expression of 209 genes in biopsies of kidney transplant patients with AR with the NanoString^® nCounter^® analysis system. With this novel technique, only low quantities of RNA from formalin fixed paraffin embedded (FFPE) biopsies are required and no amplification is needed. Therefore, residual material used for histopathological diagnosis can be analyzed. The objectives of this study were: i) to examine the gene expression profile in biopsies of patients with acute T cell-mediated rejection (aTCMR) versus patients without aTCMR and ii) to compare the gene expression profiles in patients with aTCMR treated with tacrolimus versus patients treated with belatacept.

Materials and Methods

Biopsies from 21 kidney transplant were studied. Seven biopsies from patients with aTCMR (Banff 1b-3, without C4d) treated with tacrolimus as maintenance immunosuppressive therapy, 9 biopsies from patients with aTCMR treated with belatacept, and 5 negative controls (for-cause biopsies without histomorphological changes) were included. Patients were matched for age, days after transplantation and Banff 2015 category. RNA was extracted from FFPE biopsies and gene expression was analyzed using the NanoString^® nCounter^® analysis system. Gene expression was identified by scaled estimates (JMP, Fit Model). P values were corrected for false discovery (JMP, addin)

Results and Discussion

A distinct pattern was seen in biopsies with aTCMR compared to biopsies without rejection. Comparison of aTCMR and controls identified 60 genes with higher expression (FDRPV

Conclusion

Gene expression analysis on FFPE biopsies with the novel technique NanoString^® nCounter^® analysis system can distinguish kidney transplant biopsies showing aTCMR from those of without aTCMR. Interestingly, we found no differences in gene expression profiles in renal allograft biopsies showing aTCMR in subjects receiving tacrolimus or belatacept-based immunosuppressive regimens.