title: Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining.
abstract: Anti-HLA alloantibody is a risk factor for graft loss, but does not indicate which kidneys are experiencing antibody-mediated rejection (ABMR). C4d staining in biopsies is specific for ABMR but insensitive. We hypothesized that altered expression of endothelial genes due to alloantibody acting on the microcirculation would be sensitive indicator of ABMR. We identified 119 endothelial-associated transcripts (ENDATs) from literature, and studied their expression by microarrays in 173 renal allograft biopsies for cause. Mean ENDAT expression was increased in all rejection but was higher in ABMR than in T-cell-mediated rejection and correlated with histopathologic lesions of ABMR, and alloantibody. Many individual ENDATs were increased in ABMR and predicted graft loss. Kidneys with high ENDATs and antibody showed increased lesions of ABMR and worse prognosis in comparison to controls. Only 40% of kidneys with high ENDAT expression and chronic ABMR or graft loss were diagnosed by C4d positivity. High ENDAT expression with antibody predicts graft loss with higher sensitivity (77% vs. 31%) and slightly lower specificity (71% vs. 94%) than C4d. The results were validated in independent set of 82 kidneys. High renal endothelial transcript expression in patients with alloantibody is indicator of active antibody-mediated allograft damage and poor graft outcome.
authors.affiliation: Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada. bsis@ualberta.ca
authors.forename: Banu
authors.initials: B
authors.lastname: Sis
authors.forename: Gian S
authors.initials: GS
authors.lastname: Jhangri
authors.forename: Sakarn
authors.initials: S
authors.lastname: Bunnag
authors.forename: Kara
authors.initials: K
authors.lastname: Allanach
authors.forename: Bruce
authors.initials: B
authors.lastname: Kaplan
authors.forename: Philip F
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D016000:Cluster Analysis; D004727:Endothelium / Q000378:metabolism*; D015870:Gene Expression; D006085:Graft Survival; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000235:genetics; D016030:Kidney Transplantation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007518:Isoantibodies; D012333:RNA, Messenger