P155 Defining the hierarchies of serogenic HLA allotypes discovers key hla types that warrant matching for kidney transplantation

Aim To study the ability of 121 core HLA allotypes in provoking antibody (Ab) production upon distinct exposures to identify the vigorous serogenic HLA allotypes that deserve matching in kidney transplantation. Methods HLA-Abs were analyzed in 277 patients (44% females) waiting for 2nd-kidney transplantation (Ktx), who had no HLA-Ab at pre-1st Ktx. The frequency and strength (mean of composite MFIs) of 1st Ktx-induced HLA-Abs were compared with those from patients who had u003e1 Ktxs (n = 148), and patients waiting for the 1st-Ktx (1477 females - pregnancy-induced Abs and 2274 males - naturally occurring Abs). Single antigen beads were used to assay HLA-Abs (One Lambda). Results The most prominent Abs (most frequent and strongest) produced by 1st-Ktx are DQ-specific (Fig. 1). The hierarchy of 1st-Ktx-induced Abs based on prominence is DQ3 u003e B76 u003e DQ4 u003e DQ6 u003e DQ2 u003e B45 u003e B57 u003e DR9 u003e A1 u003e DQ5 u003e DR7 u003e B58 u003e A24 u003e DR53 u003e B49 u003e B82 u003e A11 u003e B44 u003e A69 u003e A2 u003e A23 u003e A68 u003e A25 u003e A32 u003e B7C u003e A10C u003e B5C u003e DR52C u003e DR51C u003e Cw/DP. No gender-specific deviation was noted implying that prior pregnancies do not aggravate HLA-Ab production post-Ktx. The constellation of HLA-Ab in patients who had u003e1 Ktx is comparable to those had a single Ktx (Fig. 2), indicating that multiple Ktx do not exacerbate the serogenicity of HLA types. The most abundant pregnancy-induced Abs are HLA-B and A2 CREG-specific (Fig. 3). Over 60% of males waiting for 1st-Ktx have no HLA-Ab. The following Abs are detected at a frequency of 2–5% in these unsensitized males, and hierarchy built on prominence is B76 u003e B45 u003e Cw15 u003e B82 u003e Cw1 u003e B44 u003e Cw12 u003e DQ7 u003e A80 u003e B57 u003e B8 u003e B81 u003e A25 u003e Cw17 u003e B7 u003e A66 u003e A31 u003e B37 u003e A26(Fig. 4). Most of these Abs were Conclusions HLA-DQ, DR53 CREG, and A2 CREG antigens are most aggressive Ab inducers following Ktx and thus to be considered for matching. Priority for HLA-B and A2 matching will benefit females as they are strong serogenic during pregnancy. HLA-Abs detected in unsensitized males require additional scrutiny. Download high-res image (297KB) Download full-size image