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

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 r 2  = 0.6 and p  −29 (see figure). DQ3 is the most frequently and strongly encountered Abs and thus DQ3 is the most aggressive antibody inducer following Ktx. DR53 group of antigens (except DR4) and A2 CREG are the next most aggressive Ab inducers. The hierarchy from the strongest inducer is DQ9 u003e DQ8 u003e DQ7 u003e B76 u003e DR9 u003e DQ4 u003e B45 u003e DQ6 u003e B57 u003e DQ2 u003e A1 u003e DQ5 u003e DR7 u003e B57 u003e B58 u003e A24 u003e B49 u003e DR53 u003e A2 u003e B82 u003e B44 u003e A96 u003e A23 u003e A11 u003e 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 u003e A10 u003e B5 u003e DR52 u003e 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 u003e B63 u003e B73 u003e B62 u003e B75 u003e B78 u003e 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.