Advancing precision in histocompatibility and immunogenetics: a comprehensive review of the UCLA exchange program

Abstract

Precise typing of human leukocyte antigens (HLA) is crucial for clinical hematopoietic stem cell and solid organ transplantations, transfusion medicine, HLA-related disease association, and drug hypersensitivity analysis. The UCLA Cell Exchange program has played a vital role in providing educational and proficiency testing surveys to HLA laboratories worldwide for the past 5 decades. This article highlights the significant contribution of the UCLA Cell and DNA Exchange Programs in advancing HLA antibody testing, genotyping, crossmatches, and, more recently, virtual crossmatches. Additionally, we discuss future directions of the UCLA Cell Exchange program to support histocompatibility testing to adapt to the fast-evolving field of immunotherapy, tolerance and xenotransplantation.

Keywords: HLA; HLA antibody; KIR; MICA; physical crossmatch; virtual crossmatch.

FIGURE 1

The UCLA cell Exchange Program. The UCLA cell Exchange Program was first established in 1974 followed by serum exchange in 1981. In 1987, HLA class II typing was initiated with first shipment of two lymphoblastoid cell lines. By 1990, DNA typing, including restriction fragment length polymorphism (RFLP), PCR-sequence-specific primer (PCR-SSP) and PCR-sequence-specific oligonucleotide probe (PCR-SSOP) was implemented in the HLA DNA exchange survey, which became the first graded proficiency test service offered by the UCLA Exchange program in 1993. Subsequently, PCR-sequencing-based typing (PCR-SBT) was added 1996. In 2016, the exchange program embraced cutting-edge methodologies for the next-generation sequencing (NGS) HLA tying.

FIGURE 2

UCLA Virtual Crossmatch Exchange Survey. UCLA VXM Exchange consist of two Phases. In Phase I, two serum samples and three virtual donors are provided to the laboratories to perform SAB tests and 6 VXM. In Phase II, four recipient serum samples and lymphocytes from two donors are provided to perform SAB tests and 8 FXM. In Phase II, one recipient-donor pair will be selected from the VXM of Phase I, therefore a direct comparison between FXM and VXM can be achieved. VXM, virtual crossmatch; SAB, single antigen bead test; FXM, flow cytometry crossmatch; MFI, median fluorescence intensity.