A perspective on ABO incompatible transplantation

ABO blood group compatibility is a critical factor in solid organ and haemopoietic stem cell transplantation. In ABO-incompatible (ABOi) transplantation, recipient anti-A and/or anti-B antibodies may bind to donor red cell or endothelial A and B antigens triggering complement activation, potentially leading to antibody-mediated rejection (ABMR) and early graft loss. Measurement of these isohaemagglutinins by antibody titration is therefore essential for assessing transplant suitability and guiding desensitisation strategies. However, a major limitation of ABO antibody titration is the lack of international standardisation. Multiple assay platforms and variations in techniques, reagents, incubation conditions and endpoint definitions lead to significant inter-laboratory variability, potentially influencing transplant eligibility decisions and clinical outcomes. This review examines current laboratory issues associated with ABO antibody titration, including methodological variability, interpretation of titres, and biological factors influencing antibody expression. Alternative analytical and evolving approaches including flow cytometry-based assays, solid-phase platforms and complement-binding antibody testing are also discussed. Finally, future directions are considered, including assay standardisation, improved risk stratification, molecular ABO typing technologies, modification of ABO antigen expression, and international collaboration to improve the reliability of ABO antibody assessment and transplant outcome in ABO-incompatible kidney and stem cell transplantation.