Complement Polymorphisms in Kidney Transplantation: Critical in Graft Rejection?

Abstract

The complement system, as part of the innate immune system, plays an important role in renal transplantation. Complement is involved in the protection against foreign organisms and clearance of apoptotic cells but can also cause injury to the renal allograft, for instance, via antibody binding or in ischemia-reperfusion injury. Numerous polymorphisms in complement factors have been identified thus far; some of them result in different functionalities or alter complement levels. In this review, we provide an overview of the literature on the role of complement polymorphisms in renal transplantation. Furthermore, we discuss functional complement polymorphisms that have not yet been investigated in kidney transplantation. By investigating multiple polymorphisms both in donor and recipient at the same time, a complotype can be constructed. Because the combination of multiple polymorphisms is likely to have a greater impact than a single one, this could provide valuable prognostic information.

Genetic susceptibility to delayed graft function following kidney transplantation: a systematic review of the literature

“…Ficolin (FCN)-2 is an activator of the complement system via the lectin pathway. Complement activation plays a substantial role in I/R injury at the time of KTx [ 27 , 39 ]. The FCN-2 rs7851696 T allele is known to be associated with increased affinity of lectin-2 for carbohydrate structures presented by different pathogens [ 54 ].…”

“…Focusing on the complement cascade at the time of renal I/R, Michielsen et al . [ 39 ] recently summarized the impact of complement polymorphisms on kidney graft outcomes without detailing their influence on DGF occurrence. Dabrowska-Zamojcin et al .…”

“…However, complement cascade may also aggravate I/R injury via antibody binding, which eventually leads to poor outcomes after KTx. In particular, a crucial role is suspected for mannose binding lectin (MBL) in the early pathophysiology of renal I/R [ 39 ]. Nevertheless, there was no significant difference in the incidence of DGF in recipients with low MBL levels (≤400 ng/mL) compared to those with high MBL levels [ 57 ].…”

“…The present review highlights the state of knowledge in the field of genetic susceptibility to renal I/R. Although SNPs may only have minor impacts per se on gene expression and protein function, interactions among multiple SNPs may have a major impact on molecular cascades [ 39 ]. Additionally, some SNPs show very low frequency [ 31 ].…”

Association Between Promoter Polymorphisms in CD46 and CD59 in Kidney Donors and Transplant Outcome

“…Multiple studies on complement polymorphisms in kidney transplantation, including in C3, C4, and mannose-binding lectin, have been performed, but could not provide an indisputable association between these polymorphisms and acute rejection nor graft survival ( 12 ). We hypothesize that polymorphisms in genes encoding for membrane bound complement regulatory proteins in kidney donors may have a greater influence on acute rejection and graft survival because of their pivotal role in accommodation.…”