Aim: ABO-A2-incompatible transplantation (ABO-A2i Tx) for ABO-B recipients is a UNOS/OPTN policy aimed to address inequities in access to renal transplantation due to blood group. Difficulty establishing anti-A titre thresholds and/or determining patient eligibility are barriers to implementing these programs, which shorten wait times for ABO-B recipients. Red blood cell (RBC) titres are known to be plagued by lack of both reproducibility and method standardization. ABO-A1 RBC have A-II, III, and IV glycans whereas ABO-A2 RBC have only A-II glycans. We aimed to compare ABO-A1 and ABO-A2 RBC titres to anti-A-II ABO antibody (ABO-Ab) levels as measured by an ABO Luminex bead assay. We hypothesized that ABO-A2 RBC titres would be better predictors of A-II ABO-Ab levels than ABO-A1 titres. (ABO-A2 is used here to describe ABO-non-A1)
Method: ABO-Ab were measured in sera from ABO-B ABO-A2i Tx candidates (n=45). ABO-A1 and A2 RBC titres were measured in DTT-treated sera by anti-human globulin gel card. ABO-A glycans coupled to Luminex beads were used to measure IgG and IgM ABO-Ab levels; IgG and IgM were detected with anti-human IgG and IgM secondary antibodies (no DTT). Titres were compared to Luminex mean fluorescence intensity (MFI) results.
Results: ABO-A1 RBC titres were more highly correlated with anti-A-II IgG antibody levels than A2 RBC titres, disproving our hypothesis. Variable ABO-Ab levels were observed within each titre. 33% patients deemed ineligible by ABO-A1 titre threshold £ 8 had similar levels of anti-A-II as patients deemed eligible (Figure 1). Patients had significantly higher levels of IgG A-III and A-IV antibodies than A-II antibodies. Anti-A-II IgM antibodies did not correlate to titre, as predicted due to DTT treatment of the sera used for titres.
Conclusion: ABO-A2 RBC titres did not show better correlation with anti-A-II antibody levels in ABO-B recipients than A1 titres. IgM antibodies were present; the clinical relevance of these antibodies is unclear. There was high overlap in levels of donor-specific ABO-A-II antibodies between titres, suggesting that patients are being unnecessarily excluded from access to ABO-A2i Tx. New ABO-histocompatibility technologies such as the Luminex ABO antibody assay are needed to modernize ABO-A2i Tx immune risk assessment and have the potential to increase the donor pool for ABO-B and -O recipients.
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