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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 >1 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 > B76 > DQ4 > DQ6 > DQ2 > B45 > B57 > DR9 > A1 > DQ5 > DR7 > B58 > A24 > DR53 > B49 > B82 > A11 > B44 > A69 > A2 > A23 > A68 > A25 > A32 > B7C > A10C > B5C > DR52C > DR51C > 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 >1 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 > B45 > Cw15 > B82 > Cw1 > B44 > Cw12 > DQ7 > A80 > B57 > B8 > B81 > A25 > Cw17 > B7 > A66 > A31 > B37 > 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 : Download high-res image (297KB) Download : Download full-size image |
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