Molecular signatures and clinical outcomes of transplant glomerulopathy stratified by microvascular inflammation and donor‐specific antibody

Background We investigated clinical outcomes and molecular signatures of transplant glomerulopathy (TG) stratified by microvascular inflammation (MVI) and donor‐specific antibody (DSA) status. Methods We performed a retrospective review of 749 kidney transplant patients who received a for‐cause kidney biopsy from 2009 to 2014. We classified TG as MVI positive (MVI+) or MVI negative (MVI−), and with or without DSA. We obtained gene expression profiles for 44 biopsies by Affymetrix HuGene 1.0 ST expression arrays. Results A total of 100 patients had TG; 49 were MVI+, and 51 were MVI−. After a median post‐biopsy follow‐up of 2.08 years (range 0.43‐4.59), Kaplan‐Meier survival analysis demonstrated worse allograft survival in MVI+ TG patients compared with MVI− TG patients ( P  = 0.01), and time to graft failure was significantly shorter in MVI+ patients (1.08 ± 1.01 years vs 2.3 ± 1.8 years; P  = 0.002). DSA status did not affect graft survival within MVI+ or MVI− groups. Analysis of pathogenesis‐based transcripts (PBT) showed that MVI+ TG biopsies had increased expression of gamma interferon and rejection (GRIT) and DSA‐associated transcripts (DSAST), as observed in antibody‐mediated rejection. MVI− TG biopsies had increased expression of cytotoxic and regulatory T cell‐ and B cell‐associated transcripts but not GRIT or DSAST. DSA status had no effect on expression of any PBTs studied in MVI− TG biopsies. Conclusions Graft survival in TG is significantly worse in the presence of MVI. Gene expression profiles of MVI+ TG resemble antibody‐mediated rejection while gene expression profiles of MVI− TG resemble cell‐mediated rejection regardless of DSA status.