OR15 Hierarchy of HLA types in provoking antibody production following kidney transplantation

Abstract

Aim HLA antigens are diverse in cell surface expression, peptide presentation, binding immune receptors, and in eliciting immune responses. Here we examined the ability of distinct HLA types in inducing antibody (Ab) production following kidney transplantation (Ktx). Methods A cohort of 308 candidates (44% female) waiting for 2nd Ktx was studied. Prior to 1st Ktx, all were negative for HLA Abs by One Lambda single antigen bead (OL-SAB) assay. HLA Abs were measured in pre-2nd tx sera using OL-SAB. The strength (mean of MFIs) and frequency of each Abs in pre-2nd tx sera of 308 candidates were determined and plotted. Results A positive linear correlation was observed between Ab strengths to frequency with an r2 = 0.6 and p DQ8 > DQ7 > B76 > DR9 > DQ4 > B45 > DQ6 > B57 > DQ2 > A1 > DQ5 > DR7 > B57 > B58 > A24 > B49 > DR53 > A2 > B82 > B44 > A96 > A23 > A11 > A68. All HLA-Cw antigens and a subset of DPB antigens (DP15, DP13, DP5, DP1, DP23, DP4) induce Ab production at low levels and low frequency. Within Cw types, the most poorly immunogenic represents to be those carrying C1 epitope that binds to KIR2DL2/L3. The moderate inducer includes most HLA-B, HLA-A and DR antigens, and the hierarchy from the strongest inducer within this group is B7 > A10 > B5 > DR52 > DR51 CREG. The B5 CREG was diverse and observed to have four outliers from the linear fit. The strongest to weakest to trigger Abs in B5 CREG is ordered as follows: B76 > B63 > B73 > B62 > B75 > B78 > B46. Conclusions Our findings categorize 121 HLA types into three hierarchical sets based on their ability in eliciting Ab production following Ktx – strongly immunogenic, moderately immunogenic, and poorly immunogenic. The strongly immunogenic HLA types should be considered for matching in Ktx, while the poorly immunogenic HLA antigens are tolerable.