Location, Location, Location - Does Epitope Matching Matter in Pediatric Heart Transplantation?

Purpose Recent data in adult solid organ transplantation suggest that epitope-based human leukocyte antigen (HLA) matching may permit better risk assessment of de novo donor‐specific antibody (dnDSA) development compared to antigen-based HLA matching, but data in pediatric heart transplantation (PHTx) are scarce. We evaluated the association between epitope mismatches and dnDSA in PHTx. Methods We performed high resolution HLA typing and epitope mismatch analysis (HLA Matchmaker) in children undergoing primary PHTx at a single center from 2014 - 2020. DSA >1000 MFI (Luminex Single Antigen Bead Assay; One Lambda) were considered positive. Data are presented as median (interquartile range). Results Epitope and dnDSA data were available in 109 transplants (age 5.8 years [1-12], 66% male, 32% non-Hispanic White, follow-up 2.5 years [1.3 - 4.7]). There was significant diversity in the number of epitope mismatches within each HLA locus (Fig 1A), and the number of mismatches were: A 20 (13-28), B 17 (12-22), C 10 (6-15), DR 16 (8-30), DQ 12 (8-16), and DP 8 (3-13). The number of epitope mismatches did not differ among any donor-recipient race combination (not shown). The development of dnDSA was not associated with a higher number of epitope mismatches at any HLA-loci (Fig 1B). However, patients with antibody mediated rejection (AMR) had more DQ mismatches (15 vs 11; p=0.04) than those without AMR, and there were more anti-DQB1 DSA than any other DSA in the cohort (Figure 1C). Conclusion There is significant variability in the number of HLA epitope mismatches within each HLA locus. These data suggest that it may not be the total number of epitope mismatches but rather epitope mismatches at specific loci that vary in location and function that are of immunogenic importance. Further investigation of epitope-matching in PHTx may permit a more personalized immunosuppressive approach based on individualized alloimmune risk assessment in the future.