Review articleCritical evaluation of a possible role of HLA epitope matching in kidney transplantation
Section snippets
Structural and functional description of HLA epitopes
HLA epitopes are defined as the specific portions of an HLA molecule to which antibodies or T-cell receptors (TCR) bind with their paratopes [1]. An antibody paratope consists of three light-chain and three heavy-chain complementarity determining regions (CDR-L1, −L2, −L3, H1, H2, and H3). A “structural” antigen epitope, consisting of 15–22 amino acids, constitutes the whole binding site for antibodies [13], whereas the 2–5-amino-acid-long functional epitope determines the specificity of
A possible role of HLA epitope matching in kidney transplantation
Table 2 summarizes the studies examining the association between epitope mismatches and clinical outcomes in kidney transplantation. An analysis of United Network for Organ Sharing (UNOS) and Eurotransplant kidney transplant databases between 1987 and 1999 demonstrated that HLA-A and B mismatched kidneys with lower triplet mismatch numbers exhibit almost identical graft survival rates as the zero HLA-A and B antigen mismatched kidneys [28]. Laux et al. found no significant association between
Typical errors
One major critical issue in the evaluation of the superiority of epitope matching over the currently used traditional HLA-A, B, −DR matching is that epitope mismatches by definition correlate with the traditional HLA mismatches and show a collinearity. The consequence is that all clinical outcomes and side effects that are associated with the traditional HLA matching can also be demonstrated with epitope matching. Both HLA as well as epitope matching is based on genetic differences between the
Antigenicity and immunogenicity of HLA epitopes
Unfortunately, the current approaches are insufficient to predict the antigenicity and immunogenicity of HLA epitopes in a specific donor-recipient pair. Our so far obtained results indicate that certain HLA epitope mismatches appear to be more immunogenic than others to drive an alloantibody response [26]. As mentioned earlier, Laux et al. were not able to demonstrate the effect of triplet matching on graft survival on the basis of previously defined immunogenic triplet mismatches.
Future aspects of HLA epitope matching
Considering all fields of application, it is important to wait for further long-term results and to take into account currently existing limitations. Both B- as well as T-cell epitope algorithms might be further improved and combined to deeply understand alloreactivity. Before the current allocation system is shifted to epitope matching, it has to be demonstrated that this method is significantly superior to the conventional HLA matching. Adapting epitope matching to evaluation of zero or only
Conclusions
In conclusion, HLA epitope matching is an attractive candidate to improve assessment of donor-recipient HLA compatibility. A higher epitope load was reported to be associated with dnDSA development, AMR and poor graft survival in recent studies. If its superiority to conventional HLA matching could be proven, epitope-based HLA matching has the potential to play an important role in organ allocation, identification of acceptable mismatches for sensitized patients, estimation of the sensitized
Declaration of Competing Interest
None.
Acknowledgement
We did not receive any specific grant for the content of this review from funding agencies in the public and commercial or non-profit organizations. We started however last year with the company PIRCHE on the same topic a project, which is still ongoing, and received a minor financial grant.
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Present address: Ankara University Faculty of Medicine, Department of Nephrology, Ankara, Turkey.