A New Type of Antibody-Mediated Rejection of Kidney Transplants Defined by Endothelial Changes
B Sis, GS Jhangri, S Bunnag, B Kaplan, PF Halloran. University of Alberta, Edmonton, Canada; University of Illinois, Chicago
Background: HLA antibody is a risk factor for kidney transplant loss due to antibody-mediated rejection (ABMR) but is not specific for ABMR. C4d staining of peritubular capillaries in biopsies is specific for ABMR but insensitive. We hypothesized that, in biopsies from patients with HLA alloantibody, altered expression of endothelial genes would detect ABMR negative for C4d.
Design: We identified 119 endothelial cell-associated transcripts (ENDATs) from the literature. We studied 173 consecutive renal allograft biopsies for cause, using microarrays to examine the relationship of ENDAT expression to HLA antibody, pathology, and survival.
Results: Mean ENDAT expression was increased in C4d positive ABMR and correlated with pathologic lesions and HLA antibodies. Many individual ENDATs were increased in C4d positive ABMR vs. T cell-mediated rejection, and correlated with increased graft failure, particularly von Willebrand's factor (VWF). In patients with HLA antibodies, ENDATs identified C4d negative biopsies that resembled C4d positive ABMR, with transplant glomerulopathy, increased scarring, and increased graft loss, although with less inflammation. C4d positive and C4d negative ABMR accounted for most of the graft losses (14/17).
Figure 1. Graft pathology and survival in biopsies grouped according to the presence of Ab (A), C4d (C), and increased VWF expression (E).
Conclusions: In biopsies from patients with HLA antibodies, increased expression of endothelial transcripts was associated with features of ABMR and subsequent graft loss (sensitivity 91% and 79%, respectively) whether C4d was positive or negative. Compared with C4d, endothelial transcripts in biopsies represent a sensitive approach for detecting kidney transplants at risk for alloantibody-mediated deterioration.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 238, Tuesday Morning