Abstract
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.
Original language | English (US) |
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Article number | e13469 |
Journal | Clinical Transplantation |
Volume | 33 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2019 |
Keywords
- kidney transplant
- microarray
- transplant glomerulopathy
ASJC Scopus subject areas
- Transplantation