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FP7 BIOMARGIN: small sets of urinary cell mRNAs leading to a partition tree on kidney allograft lesions
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International audience. Background: FP7 Biomargin aimed at detecting and validating biomarkers of kidney graft lesions. In this study, we investigated the diagnostic potential of microRNAs (miRNAs) in allograft biopsy samples.Methods/Materials: Biopsies were collected from protocol or for-cause biopsies in 4 European clinical centers. Samples were retrospectively selected after centralized histological reading by expert pathologists, and classified into 4 groups (Normal, ABMR, TCMR or IF/TA), to build two independent case control studies (discovery- and selection sets). Global miRNA profiling was performed by microfluidic cards (TLDA, Life Technologies) on the discovery set. A statistical pipeline including 2 uni- and 5 multivariate analyses was applied to identify an extended list of biomarker candidates associated with one of the 4 groups. This extended list of miRNAs was quantified using custom TLDA plates on the selection set. Multivariate models were then built to define miRNA signatures of graft lesions.Results: A total of 754 miRNAs was quantified in the discovery set that included 32 Normal, 13 TCMR, 25 IF/TA and 18 ABMR samples. Our statistical pipeline identified 140 candidates that were assessed in the validation cohort of 32 Normal, 13 TCMR, 26 IF/TA and 28 ABMR samples. The table shows the association between histological phenotypes and miRNA-derived statisticalmodels in the validation cohort.Conclusion: We identified a small set of miRNAs within kidney allograft biopsies with a strong association with TCMR and ABMR. These miRNA signatures might provide useful molecular tools to improve allograft assessment. Their diagnostic performance is currently being investigated in our BIOMARGIN trans-sectional study of 312 consecutive allograft samples.
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