(314) Is High-Level Donor Specific Antibody Against Public Epitope a Contraindication for Kidney Transplantation?

Body: An unrelated living donor was approved for a 40-year-old male candidate for kidney retransplantation. The preliminary flow cytometric crossmatches (FCXM) was negative and there was no DSA (sample 9/19/24, Figure 1A). Four months later, the surgery was scheduled and patient was tested again for HLA antibody and FCXM. Unexpectedly, a new DSA against HLA-A25 was detected at a high level (MFI~6000, Figure 1B). However, FCXM remained negative. The discordance between two assays may be explained by following possible causes: 1) wrong sample, 2) false positive antibody, 3) low- or non-expression of donor A25 antigen, 4) factor interfering IgG antibody binding A25 antigen, 5) technical issue of FCXM, and 6) low binding of antibody on cell surface. To rule in/out these possibilities, we conducted a series of tests. First, we performed phenotype bead assay (Figure 1C) and tested another separately drawn specimen (Figure 1D). The two samples showed the similar antibody profile and further analysis revealed that these novel antibodies may be an antibody against a public epitope (group 5056E, recognizing 246S), which was confirmed by reactivity pattern in PRA assay. Accordingly, the possibilities of wrong sample and false antibodies were ruled out. To determine if the donor has a low- or non-expression of A25 allele, we performed high-resolution typing on donor and FCXM with a HLA-A25-positive surrogate donor. The NGS typing ruled out null allele and surrogate FCXM was also negative. To explore the possible interfering factor and FCXM technical concern, we also performed surrogate crossmatches with a newer specimen (2/5/25) for both FCXM and CDC with and without DTE treatment. While the A25 antibody remained at a "high" level (MFI>6500, Figure 1E), all crossmatches were negative. Taken together, the HLA-A25 antibody level may be reflected falsely higher in SAB assay than its actual level, and/or such antibody may not bind well the cell surface A25 antigen. Collectively, it was decided to proceed transplantation with close monitoring of DSA post-transplant.

Conclusion: This case highlights that DSA even showing pattern against public epitope with a high MFI may not necessarily be a contraindication for kidney transplantation, if FCXM is consistently negative and sample error, technical issue and interfering factor can be ruled out.