Abstract
CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.
Highlights
Kidney transplantation is the preferred treatment option for many patients with end-stage kidney disease
This study included 190 recipients who were transplanted with a kidney from a deceased donor between 1995 and 2005 and who did not have pre-transplant donorspecific human leukocyte antigen (HLA) antibodies (DSA), but had antibodies against other HLA antigens
As a surrogate marker for donor-reactive memory T-helper cells, we here evaluated whether the potential presence of T-cell epitopes shared between immunizing and recall HLA would affect the risk of kidney graft failure
Summary
Kidney transplantation is the preferred treatment option for many patients with end-stage kidney disease. The outcome of such a treatment is most optimal when recipient and donor are human leukocyte antigen (HLA) matched [1, 2]. Through the activation of alloimmune T and B cells, HLA mismatches may lead to T-cellmediated rejection, or, via the development of donorspecific HLA antibodies (DSA), to antibody-mediated rejection [3]. A mismatched HLA allele may lack immunogenic epitopes capable of inducing an alloimmune response. Epitopes that are specific for the mismatched HLA of the donor, and absent in HLA of the recipient, can potentially elicit an alloimmune response [15]. Various algorithms have been developed for prediction of HLA matching based on B-cell epitopes, such as HLA‐EMMA and HLAMatchmaker [16, 17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
