BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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HLA-DP 错配和供体特异性 HLA-DP 抗体在肾移植中的作用：病例系列。

背景 HLA-DP 错配对同种异体肾移植结果的影响仍然知之甚少，并且被认为低于其他 HLA 基因座的影响。HLA-DP 供体特异性抗体 (DSA) 与其他 DSA 的共同关联排除了对 HLA-DP DSA 实际效果的评估。方法 从大型多中心数据收集中，我们回顾性评估了 HLA-DP DSA 对移植结果的意义以及 HLA-DP eplet 错配对 HLA-DP DSA 诱导的免疫原性。此外，我们评估了在 Luminex 测定中检测到的 HLA-DP 抗体的 MFI 与流式细胞术/补体依赖性细胞毒性 (CDC) 交叉匹配结果之间的关联。结果 在移植前分离出 HLA-DP 抗体的患者（N = 13）中，6 名患者经历了抗体介导的排斥反应 (AMR)，3 名患者失去了移植物。在 HLA-DP 错配 (N = 72) 的 HLAMatchmaker 分析中，在所有 84DEAV (N = 14) 的病例中，在 86% 的 85GPM (N = 6/7) 病例中，在停止免疫抑制后出现 HLA-DP DSA，在50% 的病例为 56E (N = 6/12)，40% 的病例为 56A 不匹配 (N = 2/5)。分离的 HLA-DP DSA MFI 和交叉配型（N = 90）之间的相关性分析显示 HLA-DP DSA MFI <2000（N = 14）的负交叉配型结果。低于 10,000 个 CDC 交叉匹配的 MFI 也是阴性的（N = 33）。在这些 MFI 值之上，生成了正 (N = 35) 和负 (N = 16) 交叉匹配结果。结论 孤立的 HLA-DP DSA 很少见，但对 AMR 构成重大风险。我们确定了可能导致 HLA-DP DSA 形成的高风险 eplet 错配。因此，我们建议在移植前进行 HLA-DP 分型以进行 HLA-DP DSA 分析。具有高 MFI 的 HLA-DP DSA 并不总是与阳性交叉配型结果相关。