The science of compatibility: A comprehensive review of crossmatch techniques in organ transplantation

Abstract

Crossmatch technologies have revolutionised transplant immunology by improving the evaluation of donor-recipient compatibility and enhancing transplant outcomes. Complement-dependent cytotoxicity Crossmatch was a foundational method to detect cytotoxic antibodies, but its limited sensitivity and specificity prompted advancements. Flow Cytometry Crossmatch offered significant improvements, detecting both complement-fixing and non-complement-fixing antibodies, thus providing stronger correlations with graft survival. Solid Phase Immunoassays, including enzyme-linked immunosorbent assays and bead-based platforms, introduced recombinant human leukocyte antigen molecules, enabling higher sensitivity and specificity while minimising false positives. These assays allow qualitative and semi-quantitative assessments of donor-specific antibodies, facilitating informed transplantation decisions. The emergence of Virtual Crossmatching has transformed the field by enabling rapid, computer-based evaluation of donor-recipient compatibility, significantly reducing delays in organ allocation. Additionally, the calculated Panel Reactive Antibody metric refines recipient sensitisation assessments by incorporating extensive donor data, leading to improved compatibility estimates and better clinical outcomes. These advancements have reduced rejection rates, optimised organ allocation, and enhanced graft survival. This review underscores the profound impact of evolving crossmatch methodologies on transplantation while highlighting the potential of ongoing innovations to refine compatibility assessments further and improve patient outcomes.