OR4 Possible parameters for determination of unacceptable DP antigens for transplantation

Abstract

UNOS has recently modified the Unacceptable Antigen table to allow entry of DPB1 as unacceptable antigens. Our MFI cutoffs with other HLA loci have shown good correlation with Flow crossmatch (XM) results and have allowed us to predict incompatible crossmatches with a high degree of accuracy. However, we have been unable to predict the B cell Flow crossmatch result for DP antibodies based on the MFI value in the microarray assay. This makes it difficult to enter most DP antibodies as unacceptable in UNET without ruling out many potential “compatible” donors. Aim The purpose of this study was to look at other parameters of DP that might show a better correlation with positive Flow crossmatch and thus a higher predictive value. Methods 36 crossmatch pairs with donor-specific antibody (DSA) against a DP mismatch were chosen for this study. DP antibody was identified using single antigen beads in a microarray assay (Thermo Fisher). Results Sixteen crossmatches were positive and 20 were negative. The average MFI for the DP antibody in the positive and negative crossmatch groups was 9634 and 9970, respectively. This confirmed our previous opinion that an unacceptable DP cannot be based on MFI cutoffs. We then looked at TCE grouping for DSA against DP and also the epitopes found in key DP hypervariable regions to see if there was a correlation between DP antibody responsiveness and a positive crossmatch. DPs can be grouped into three TCE groups based on T cell activity. Group 1 has high reactivity, Group 2 moderate, and Group 3 minimal reactivity. We examined the DP donor-specific antibodies and assigned each to the appropriate TCE group. 50% of the DP in Positive crossmatches were in Group 1 or 2, while only 25% of the Negative crossmatches were in Group 1 or 2. However, the correlation using the TCE groups does not seem to be strong enough for predicting crossmatch compatibility. Hypervariable regions for epitopes at positions 55–57 and 84–87 account for most of the DP serological reactivity. Review of these areas show that 93.8% of the Positive crossmatches had a DP DSA with DEAV at the 84–87 region. 65% of patients with DP DSA and a negative XM did not have DEAV at position 84–87. Conclusion The presence of DEAV at position 84–87 may be important in identifying unacceptable DP antigens.