The evolution and clinical impact of Human Leukocyte Antigen technology

Abstract

As human leukocyte (HLA) antigen and antibody testing has evolved, typing, screening, and crossmatching assays have become exquisitely specific and sensitive. How best to use this information is a focal point of the transplant community and of this review. Driven by advances in technology, two major changes in the transplant community recently occurred. Firstly, the United Network for Organ Sharing mandated the use of cPRA to replace the more subjective panel reactive antibody value. Secondly, the virtual crossmatch (vXM) became a reality. The vXM categorizes sensitized patients as compatible or incompatible with their donors by predicting the likelihood of a positive crossmatch. Although the use of cPRA and vXM represents major progress in organ allocation algorithms, there are compelling issues that must be addressed. These include defining appropriate threshold values for antibody assignment and recognizing the relevance of antibodies to HLA-Cw*, HLA-DQ*, and HLA-DP*. Undoubtedly, molecular HLA-typing and solid-phase antibody-detection assays have revolutionized clinical histocompatibility testing. These new testing methodologies have had a major impact in both allocation and outcome of transplanted kidneys. However, even these new methodologies are not flawless and pose new challenges to the transplant community.