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Molecular signatures and clinical outcomes of transplant glomerulopathy stratified by microvascular inflammation and donor‐specific antibody
Author(s) -
Lubetzky Michelle,
Hayde Nicole,
Ó Broin Pilib,
Ajaimy Maria,
Bao Yi,
Mohammed Omar,
Schwartz Daniel,
Pullman James,
Akalin Enver
Publication year - 2019
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.13469
Subject(s) - medicine , biopsy , antibody , gastroenterology , immunohistochemistry , kidney , kidney transplantation , immunology
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.