Multiplex bead immunoassay in ABO-A2-incompatible kidney transplantation
Anne Halpin, Cathi Murphey, Bruce Motyka, Caishun Li, J. Pearcey, Maria Ellis, E. Dijke, Simon Urschel, Adam W. Bingaman, Tess Van Ong, Matthias Kapturczak, Todd L. Lowary, Christopher W. Cairo, Lori J. West
Abstract
Kidney transplantation from ABO-A2 donors into ABO-O and ABO-B recipients can alleviate inequitable transplant access created by ABO demographics. ABO-A2-incompatible (ABO-A2i) eligibility is determined by anti-A hemagglutination titers. However, titers do not distinguish antibodies specific for A-II glycans, the sole A-antigen subtype in vascular endothelium, from other anti-A antibodies. We examined whether reliance on anti-A titers unnecessarily limited ABO-A2i transplants for candidates with low anti-A-II levels. We created a single-antigen bead immunoassay for ABO antibodies, confirmed the specificity and reproducibility, and demonstrated the ability to detect anti-A and anti-B glycan subtype-specific antibodies in healthy control sera. We then measured subtype-specific anti-A antibodies in original sera from ABO-B and ABO-O candidates who had been previously evaluated for ABO-A2i eligibility. Anti-A-II levels in candidates who had been deemed ineligible (anti-A titers >4) were compared to eligible candidates (anti-A titers ≤4) who had subsequently received ABO-A2i kidneys. Of 141 candidates, 75 (53%) were ineligible; 66 (47%) were eligible and received ABO-A2 kidneys. Retesting original sera, 55% (41/75) of ineligible candidates had anti-A-II levels comparable to eligible candidates. Anti-A titers did not reflect anti-A-II levels. Our ABO antibody assay reproducibly measures graft-specific anti-A-II antibodies, providing information beyond anti-A titers that may increase transplant access for ABO-B and ABO-O candidates.