Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, University Hospital, LMU Munich, Munich, Germany.
Division of Thoracic Surgery, University Hospital, LMU Munich, Munich, Germany.
Transpl Int. 2024 Sep 19;37:13010. doi: 10.3389/ti.2024.13010. eCollection 2024.
Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients ( = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR ( = 0.03) and CLAD ( = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.
人类白细胞抗原（HLA）供受者之间的错配（MM）导致肺移植（LTX）中的有效 MM（epMM），这可能导致新产生的供体特异性 HLA 抗体（dnDSA）的产生，特别是 HLA-DQ-dnDSA。本研究的目的是确定 HLA-DQ-dnDSA 发展的危险因素。我们纳入了 2012 年至 2020 年间接受 LTX 的所有患者。所有受者/供者均进行了 HLA11 位点的分型。在 LTX 后 1 年监测 dnDSA 的发展。使用 HLAMatchmaker 计算 epMM。使用 Chi2 检验和学生 t 检验比较比例和平均值的差异。我们使用 Kaplan-Meier 曲线和 LogRank 检验以及多变量 Cox 回归比较急性细胞排斥（ACR）、慢性肺移植物功能障碍（CLAD）和生存率。在 183 例患者中，22.9%的患者发生了 HLA-DQ-dnDSA。与 HLA-DQ 杂合子患者相比，HLA-DQ 纯合子患者更有可能发生 HLA-DQ-dnDSA（ = 0.03）。如果 HLA-DQ1 纯合子患者接受 HLA-DQB1*03:01 供体，他们似乎有更高的 HLA-DQ-dnDSA 发病风险。几个 DQ 有效表位与 HLA-DQ-dnDSA 的发展显著相关。多变量分析显示，HLA-DQ-dnDSA 与 ACR（ = 0.03）和 CLAD（ = 0.01）显著相关。HLA-DQ 纯合性、几种高危 DQ 组合和高危 epMM 导致 HLA-DQ-dnDSA 发展的风险增加，从而对临床结果产生负面影响。在临床实践中的实施可以改善免疫相容性和移植物结局。
