Elevated intragraft expression of innate immunity and cell death-related markers is a risk factor for adverse graft outcome

Abstract

Background: Molecules of the innate immune response are increasingly recognized as important mediators in allograft injury during and after kidney transplantation. We therefore aimed to establish the relationship between the expression of these genes at implantation, during an acute rejection (AR) and on graft outcome.

Methods: A total of 19 genes, including Toll like receptors (TLRs), complement components and regulators, and apoptosis-related genes were analyzed at the mRNA level by qPCR in 123 biopsies with acute rejection and paired pre-transplantation tissue (n = 75).

Results: Before transplantation, relative mRNA expression of BAX:BCL2 ratio (apoptosis marker) and several complement genes was significantly higher in tissue samples from deceased donors compared to living donors. During AR, TLRs and complement genes showed an increased expression compared to pre-transplant conditions, whereas complement regulators were decreased. A relatively high TLR4 expression level and BAX:BCL2 ratio during AR in the deceased donor group was associated with adverse graft outcome, independently of clinical risk factors.

Conclusions: Complement- and apoptosis-related gene expression is elevated in deceased donor transplants before transplantation. High BAX:BCL2 ratio and TLR4 expression during AR may reflect enhanced intragraft cell death and immunogenic danger signals, and pose a risk factor for adverse graft outcome.

Keywords: Apoptosis; Complement; Gene expression; Kidney transplant outcome; Toll like receptors.