Tissue typing for kidney transplantation for the general nephrologist

Abstract

This review explains the complexity and shortcomings of serological and molecular human leukocyte antigens (HLA) typing, which are critical in the assessment of immunological risks for potential kidney transplant candidates. Consequently, the determination of HLA structure using molecular typing has enabled a more accurate assessment of HLA compatibility between donors and recipients. ABSTRACT:Tissue typing is the process by which an individual's human leukocyte antigens (HLA) are determined. In transplantation, this vital process allows the immunologic or rejection risk of a donor-recipient pairing to be assessed through reviewing their HLA matching and whether any anti-HLA antibodies present in recipient serum are donor specific. Tissue typing has increased in sophistication over time which has allowed a deeper appreciation of the antigenically important parts of HLA and increased the complexity of determining immunologic risk.

Approaches for the characterization of clinically relevant pre‐transplant human leucocyte antigen (HLA) antibodies in solid organ transplant patients

“…The HLA molecule can be considered as a collection of immunogenic amino acid clusters, which are termed "epitopes" (Duquesnoy, 2014a). Epitopes consist of ~15-22 amino acid residues that can elicit an alloreactive response (Duquesnoy, 2006;Filippone & Farber, 2016;Geneugelijk & Spierings, 2020;Mulley et al, 2019;Sypek et al, 2018). Within an epitope, there are smaller structural formations of 2-5 amino acid residues (usually within a spatial radius of 3.0-3.5 Å) located close to the antigen surface (Filippone & Farber, 2016;Kramer et al, 2019;McCaughan & Tinckam, 2018;Peng et al, 2019;Zeevi et al, 2012), which determine the strength and specificity of antibody interactions.…”

“…Within an epitope, there are smaller structural formations of 2-5 amino acid residues (usually within a spatial radius of 3.0-3.5 Å) located close to the antigen surface (Filippone & Farber, 2016;Kramer et al, 2019;McCaughan & Tinckam, 2018;Peng et al, 2019;Zeevi et al, 2012), which determine the strength and specificity of antibody interactions. Each epitope includes many of these distinct functional components, commonly referred to as "eplets" (Filippone & Farber, 2015;Mulley et al, 2019;Sypek et al, 2018). While some eplets may demonstrate immunogenicity alone, others may only be immunogenic when found in conjunction with another "paired" eplet (Duquesnoy & Marrari, 2017;McCaughan & Tinckam, 2018).…”

“…Despite the high level of polymorphism seen in the HLA system, there is a high degree of conservation outside of the key polymorphic regions (Raghavan et al, 2019;Tambur, 2018). HLA antibodies are therefore targeted against structural epitopes/eplets rather than individual HLA protein mismatches (Duquesnoy, Marrari, Jelenik, et al, 2013;Duquesnoy, Marrari, da Sousa, et al, 2013;Filippone & Farber, 2016;Mulley et al, 2019). Approximately half of defined HLA Class I epitopes are shared between different HLA molecules (analogous to the "cross-reactive groups" previously defined serologically) and these are termed "public" epitopes.…”