The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation

Abstract

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and -318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the -1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.

Genetic polymorphisms in TLR3, IL10 and CD209 influence the risk of BK polyomavirus infection after kidney transplantation

“…In addition we considered SNPs for which some prior evidence suggests an involvement in BKPyV infection or BKPyVAN, such as TLR3 and TNF 18 , 32 . Finally, we included polymorphisms in the CTLA4 gene, which codes for a costimulatory receptor crucial in immune homeostasis 33 .…”

Immune Checkpoints in Solid Organ Transplantation

“…For example, the CTLA-4 rs3087243*G allele was found to be protective against TCMR in kidney transplant recipients (KTRs) [33]. Other polymorphisms were studied but with no definitive conclusion as to their effect on transplantation [34]. These studies suggest that the consequences of these polymorphisms on CTLA-4 functions may be too tenuous to emerge as independent and significant drivers of transplant rejection.…”