Spatial transcriptomics of Glomerulo-centric antibody mediated rejection in renal transplants

Abstract

In this case study, we used Digital Spatial Profiling to localize transcripts in a series of 4 biopsies from a single patient before, during and after treatment for acute antibody-mediated rejection that was characterized by strong C4d staining of the glomeruli. Spatial resolution demonstrated that molecular signatures of innate immune cells including NK cells and macrophages are located in glomeruli during AMR, and transcripts for HLA class II antigens were upregulated in the glomeruli. In contrast, transcripts of signature genes for podocytes were decreased during rejection. Treatment with IVIg resolved histological evidence of glomerulitis but did not restore expression of podocyte transcripts. These data demonstrate a vulnerability of podocytes in acute AMR with persistent glomerulitis. Additionally, by using a protocol biopsy from the same patient as a baseline, transcript changes for an informative set of genes were uncovered to test for podocyte dysfunction in future patients.