Microcirculation Endothelial Cell Proliferation Is Specifically Increased in Antibody-Mediated Rejection as Compared to Other Diseases in Kidney Transplants.
Stephen Osasan, Jessica Chang, Yasemin Ozluk, Declan G de Freitas, Michael Mengel, Phillip Halloran, Banu Sis. University of Alberta, Edmonton, Canada
Background: Antibody-mediated rejection (ABMR) is mediated by antibodies against donor HLA, leading to allograft injury and failure. We hypothesized that there is greater endothelial repair response in ABMR compared to other diseases in kidney transplants.
Design: We related microcirculation endothelial cell cycling and density of peritubular capillaries(PTC) to lesions, diagnoses, and whole-genome microarrays in 100 non-selected kidney transplant biopsies for cause(BFC) and 20 normal kidney implantation biopsies from living donors. We performed double immunostaining and quantified the microcirculation endothelial cell cycling (Ki-67+CD31+ glomerular capillaries and PTCs) and the CD31+ PTC density by cell counting in the entire renal cortical biopsy area.
Results: The BFC showed higher numbers of cycling microcirculation endothelial cells in comparison to normal controls (p=0.001). The endothelial cell cycling was specifically increased in ABMR compared to other diseases i.e. T cell-mediated rejection, glomerulonephritis, and others.
This increase correlates with microcirculation lesions (glomerulitis, peritubular capillaritis, transplant glomerulopathy), and C4d staining (p<0.05). Furthermore, It also correlates with transcript sets representing the molecular burden of active ABMR(p<0.05). The PTC density was lower in biopsies for cause when compared to normal controls (p<0.001). However, the PTC density did not differ among diagnoses and was not correlated with time post-transplant, scarring or other lesions.
Conclusions: We conclude that endothelial repair response is specifically increased in kidneys with ABMR, reflecting the burden of microcirculation injury. In contrast to previous observations, there is no evidence for reduced PTC density in kidneys with scarring.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 266, Wednesday Afternoon