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

Abstract

The avoidance of antibody-mediated rejection (AMR) attributed to human leucocyte antigen (HLA) antibody incompatibility remains an essential function of clinical Histocompatibility and Immunogenetics (H&I) laboratories who are supporting solid organ transplantation. Developments in HLA antibody identification assays over the past thirty years have greatly reduced unexpected positive cellular crossmatches and improved solid organ transplant outcomes. For sensitized patients, the decision to register unacceptable HLA antigen mismatches is often heavily influenced by results from solid phase antibody assays, particularly the Luminex® Single Antigen Bead (SAB) assays, although the clinical relevance of antibodies identified solely by these assays remains unclear. As such, the identification of non-clinically relevant antibodies may proportionally increase the number of unacceptable transplant mismatches registered, with an associated increase in waiting time for a compatible organ. We reflect on the clinical relevance of antibodies identified solely by the Luminex SAB® assays and consider whether the application of additional assays and/or tools could further develop our ability to define the clinical relevance of antibodies identified in patient sera. Improvements in this area would assist equity of access to a compatible transplant for highly sensitized patients awaiting a solid organ transplant.