Daniëls Liesbeth, Claas Frans H J, Kramer Cynthia S M, Senev Aleksandar, Vanden Driessche Marleen, Emonds Marie-Paule, Van Laecke Steven, Hellemans Rachel, Abramowicz Daniel, Naesens Maarten
Histocompatibility and Immunogenetics Laboratory (HILA), Red Cross-Flanders, Mechelen, Belgium.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Transpl Immunol. 2021 Apr;65:101287. doi: 10.1016/j.trim.2020.101287. Epub 2020 Mar 16.
The impact of HLA-DP mismatches on renal allograft outcome is still poorly understood and is suggested to be less than that of the other HLA loci. The common association of HLA-DP donor-specific antibodies (DSA) with other DSA obviates the evaluation of the actual effect of HLA-DP DSA.
From a large multicenter data collection, we retrospectively evaluated the significance of HLA-DP DSA on transplant outcome and the immunogenicity of HLA-DP eplet mismatches with respect to the induction of HLA-DP DSA. Furthermore, we evaluated the association between the MFI of HLA-DP antibodies detected in Luminex assays and the outcome of flowcytometric/complement-dependent cytotoxicity (CDC) crossmatches.
In patients with isolated pretransplant HLA-DP antibodies (N = 13), 6 experienced antibody-mediated rejection (AMR) and 3 patients lost their graft. In HLAMatchmaker analysis of HLA-DP mismatches (N = 72), HLA-DP DSA developed after cessation of immunosuppression in all cases with 84DEAV (N = 14), in 86% of cases with 85GPM (N = 6/7), in 50% of cases with 56E (N = 6/12) and in 40% of cases with 56A mismatch (N = 2/5). Correlation analysis between isolated HLA-DP DSA MFI and crossmatches (N = 90) showed negative crossmatch results with HLA-DP DSA MFI <2000 (N = 14). Below an MFI of 10,000 CDC crossmatches were also negative (N = 33). Above these MFI values both positive (N = 35) and negative (N = 16) crossmatch results were generated.
Isolated HLA-DP DSA are rare, yet constitute a significant risk for AMR. We identified high-risk eplet mismatches that can lead to HLA-DP DSA formation. We therefore recommend HLA-DP typing to perform HLA-DP DSA analysis before transplantation. HLA-DP DSA with high MFI were not always correlated with positive crossmatch results.
HLA-DP错配对肾移植结局的影响仍了解甚少，且被认为小于其他HLA基因座。HLA-DP供者特异性抗体（DSA）与其他DSA的常见关联使得对HLA-DP DSA实际效应的评估变得复杂。
从大量多中心数据收集中，我们回顾性评估了HLA-DP DSA对移植结局的意义以及HLA-DP表位错配相对于HLA-DP DSA诱导的免疫原性。此外，我们评估了在Luminex检测中检测到的HLA-DP抗体的平均荧光强度（MFI）与流式细胞术/补体依赖细胞毒性（CDC）交叉配型结果之间的关联。
在移植前仅存在HLA-DP抗体的患者中（N = 13），6例发生了抗体介导的排斥反应（AMR），3例患者移植肾失功。在对HLA-DP错配的HLAMatchmaker分析中（N = 72），在所有携带84DEAV的病例中（N = 14）、86%携带85GPM的病例中（N = 6/7）、50%携带56E的病例中（N = 6/12）以及40%携带56A错配的病例中（N = 2/5），免疫抑制停止后均产生了HLA-DP DSA。对仅有的HLA-DP DSA MFI与交叉配型结果（N = 90）进行相关性分析显示，当HLA-DP DSA MFI < 2000时（N = 14）交叉配型结果为阴性。当MFI低于10,000时，CDC交叉配型结果也为阴性（N = 33）。高于这些MFI值时，交叉配型结果既有阳性（N = 35）也有阴性（N = 16）。
孤立的HLA-DP DSA很少见，但却是AMR的重要风险因素。我们确定了可导致HLA-DP DSA形成的高风险表位错配。因此，我们建议在移植前进行HLA-DP分型以开展HLA-DP DSA分析。高MFI的HLA-DP DSA并不总是与阳性交叉配型结果相关。
