Raineri Francesca, Frischknecht Lukas, Nilsson Jakob, Rössler Fabian, Cavelti-Weder Claudia, von Moos Seraina, Schachtner Thomas
Department of Nephrology, University Hospital Zurich, Zurich, Switzerland.
Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
Transpl Int. 2024 Dec 18;37:13720. doi: 10.3389/ti.2024.13720. eCollection 2024.
The molecular HLA epitope mismatch is an advanced measure for developing donor-specific antibodies (dnDSA) after kidney transplantation. Its relevance in simultaneous pancreas/kidney transplant recipients (SPKTRs) remains unclear. We investigated dnDSA development in 72 SPKTRs and 383 kidney transplant recipients (KTRs) and used the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm to calculate the mismatch load of HLA-derived epitopes in total, per HLA-class, and per HLA-locus. At 1 year post-transplant, SPKTRs exhibited an increased dnDSA incidence (11.2% vs. 3.1%, = 0.011); but not at 10 years post-transplant. In SPKTRs, preformed DSA (HR 2.872, = 0.039) and younger donor age (HR 0.943, = 0.017) were independent risk factors for developing dnDSA. PIRCHE-II scores for HLA-DQ correlated with dnDSA development upon univariate analysis ( = 0.044). Among 455 KTRs/SPKTRs, multivariate analysis identified PIRCHE-II scores for HLA-DQ (HR 1.023, = 0.025) and ciclosporine use (HR 2.440, = 0.001) as independent predictors of dnDSA development. Simultaneous pancreas/kidney transplantation (SPK) was an independent risk factor in case of preformed DSA only (HR 2.782, = 0.037). High PIRCHE-II scores for HLA-DQ are crucial for dnDSA development in both SPKTRs and KTRs. The lack of an independent association of total PIRCHE-II scores urges caution in implementing it in post-transplantation risk assessment.
分子 HLA 表位错配是肾移植后产生供体特异性抗体（dnDSA）的一种先进检测方法。其在同期胰肾联合移植受者（SPKTR）中的相关性仍不明确。我们调查了 72 例 SPKTR 和 383 例肾移植受者（KTR）中 dnDSA 的产生情况，并使用预测间接可识别 HLA 表位（PIRCHE-II）算法来计算 HLA 衍生表位在总体、每个 HLA 类别和每个 HLA 位点的错配负荷。移植后 1 年时，SPKTR 的 dnDSA 发生率升高（11.2% 对 3.1%，P = 0.011）；但移植后 10 年时并非如此。在 SPKTR 中，预存 DSA（风险比 2.872，P = 0.039）和供体年龄较小（风险比 0.943，P = 0.017）是发生 dnDSA 的独立危险因素。单因素分析时，HLA-DQ 的 PIRCHE-II 评分与 dnDSA 的产生相关（P = 0.044）。在 455 例 KTR/SPKTR 中，多因素分析确定 HLA-DQ 的 PIRCHE-II 评分（风险比 1.023，P = 0.025）和使用环孢素（风险比 2.440，P = 0.001）是 dnDSA 产生的独立预测因素。仅在存在预存 DSA 的情况下，同期胰肾联合移植（SPK）是一个独立危险因素（风险比 2.782，P = 0.037）。HLA-DQ 的高 PIRCHE-II 评分对 SPKTR 和 KTR 中 dnDSA 的产生至关重要。PIRCHE-II 总分缺乏独立相关性，这促使在移植后风险评估中应用该评分时要谨慎。
