P112 Impact of allele-specific anti-HLA class I antibodies on organ allocation

Abstract

Aim Accurate classification of serologically-distinct antigens (Ag) is critical in organ allocation, and nowadays it is possible to define anti-HLA antibody specificity to the allelic level. We examined class I antibodies (Ab) for allelic specificities that may be serologically distinct and evaluated its impact on crossmatch (XM) results and organ allocation. Methods 6726 sera were tested for anti-HLA Ab using LABScreen Single Ag assay (One Lambda), in which 17 class I HLA Ag are represented by more than one allele. Discordance in MFI values between the two allelic beads was examined as a categorical variable to mimic clinical practice, and as a continuous variable (MFI value) to better reflect biological plausibility. To evaluate the significance of an allele-specific Ab on XM results, we examined an unbiased cohort of deceased donor-candidate testing (125,828 CDC XMs between 2014 and 2017). In our lab, all candidates within a blood group have a CDC XM performed, regardless of whether they have donor-specific antibody (DSA). This uniquely allows us to examine whether a candidate with an allele-specific DSA, who has already been excluded from the match run, would indeed have a positive XM against a donor who has a different allele. Statistical analyses were performed using JMP12Pro (SAS Institute). Results 1. The incidence of discordance between the two allelic beads varied depending on whether MFI values were considered as continuous vs categorical variables. 2. The presence of allele-specific Ab for rare alleles was out of proportion to their frequencies in the population. 3. The presence of Ab against only the rare allele was a poor predictor of a positive CDC XM, with a positive predictive value of 0–7% compared with 52.5% if the candidate had DSA against an A or B locus Ag. Conclusions 9 out of 17 Class I HLA antigens had potential allele-specific reactivity, meaning that candidates with antibody selectivity against rare alleles may be unnecessarily excluded from many organ offers based on definition of unacceptable antigens by serological equivalence. Conversely, for centers relying on virtual-XM, prematurely defining alleles as new serological splits could unfortunately allow transplants for which the recipient has DSA. Further testing is needed to rigorously confirm these allele-specific reactivity patterns.