Michelle Lubetzky1, Nicole Hayde2, Pilib Ó Broin3, Maria Ajaimy2, Yi Bao2, Omar Mohammed2, Daniel Schwartz4, James Pullman4, Enver Akalin2. 1. Weill Cornell-NY Presbyterian, Division of Nephrology, New York City, New York. 2. Montefiore Medical Center Transplant Center, Albert Einstein College of Medicine, New York City, New York. 3. School of Mathematics, Statistics & Applied Mathematics, National University of Ireland Galway, Galway, Ireland. 4. Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, New York.
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.
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+ TGpatients compared with MVI- TGpatients (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.
Authors: Candice Roufosse; Jan Ulrich Becker; Marion Rabant; Daniel Seron; Maria Irene Bellini; Georg A Böhmig; Klemens Budde; Fritz Diekmann; Denis Glotz; Luuk Hilbrands; Alexandre Loupy; Rainer Oberbauer; Liset Pengel; Stefan Schneeberger; Maarten Naesens Journal: Transpl Int Date: 2022-05-20 Impact factor: 3.842
Authors: Shannon R Reese; Nancy A Wilson; Yabing Huang; Lucille Ptak; Kenna R Degner; Ding Xiang; Robert R Redfield; Weixiong Zhong; Sarah E Panzer Journal: Transplantation Date: 2021-07-01 Impact factor: 5.385