Acute rejection (AR) is a major cause of allograft dysfunction. Molecular signatures of AR from blood and biopsy have been identified by several independent cohort studies but vary between these studies. The aim of this study was to identify meta signatures in both biopsy and blood for AR through meta-analysis of the GOCAR expression datasets combined with published datasets. From 735 biopsy samples from 7 different expression datasets, we identified 982 meta genes at FDR<0.05 by using the method of combining effect-sizes and p values. Genes involved in immune response, T cell/B cell activation, cell adhesion/proliferation were upregulated while the genes involved in metabolism were dowregulated. Pathway analysis indicated that pathways of antigen presentation, signaling of T helper cell, dendritic and natural killer cells were upregulated. The meta correlation matrix among meta genes was built from expression data of AR patients, from which 14 highly co-regulated core modules were further identified. The demographic or clinical variables/outcomes that were significantly associated with these core modules were identified from GOCAR study. From 422 blood samples from 8 expression datasets, we identified 243 meta genes associated with AR. Interestingly, the genes involved in T cell/B cell activation were down-regulated whereas immune/defense response and protein kinase cascade genes were up-regulated in AR patients compared to non-AR patients. The pathways of IL6 signaling and granzyme B signaling were down-regulated. Our meta-analysis of both biopsy and blood profiles in over 1000 kidney transplant patients revealed distinct dysregulated molecular signatures/modules and pathways associated with AR, which may shed light on the understanding of molecular mechanism of acute rejection and development of proper immune therapy to AR treatment.

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