Tian Yuan, Frischknecht Lukas, Mallone Anna, Rössler Fabian, Schachtner Thomas, Nilsson Jakob
Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland.
Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland.
Front Immunol. 2025 Jan 16;15:1530065. doi: 10.3389/fimmu.2024.1530065. eCollection 2024.
Donor-derived cell-free DNA (dd-cfDNA) is a promising non-invasive biomarker for detecting graft injury in solid organ transplant recipients. Elevated dd-cfDNA levels are strongly associated with rejection and graft injury, especially antibody-mediated rejection (ABMR). While donor-specific antibodies (dnDSA) are crucial in ABMR, the relationship between dd-cfDNA levels and dnDSA features, such as DSA category, MFI and HLA target loci, remains unclear.
We analyzed dd-cfDNA levels in 75 kidney transplant recipients who developed dnDSA post-transplant. dnDSA were categorized as "true", "possible", or "false" based on bead reactivity patterns and HLA typing. dd-cfDNA was assessed alongside dnDSA detection and sequential follow-up samples in a subgroup.
"True" dnDSA showed significantly higher dd-cfDNA levels compared to "possible" and "false" groups. None of the dd-cfDNA values in the "false" group exceeded 0.6%, and only a small fraction of the "possible" group had values slightly above 0.6%. dd-cfDNA levels were not significantly affected by dnDSA target loci or number. A strong correlation between cumulative dnDSA MFI and dd-cfDNA levels was observed, especially in patients with "true" HLA-DQ-directed dnDSA. Sequential dd-cfDNA analysis showed dynamic changes in 25% of patients, all from the "true" dnDSA group, which tended to align with shifts in cumulative MFI over time.
These findings highlight the correlation between cumulative dnDSA MFI and dd-cfDNA levels, particularly in HLA-DQ-directed dnDSA, and suggest graft injury is dynamic in dnDSA-positive patients. Integrated monitoring of dnDSA and dd-cfDNA offers a promising non-invasive approach for assessing graft injury and alloimmunity, potentially enhancing post-transplant care.
供体来源的游离DNA（dd-cfDNA）是检测实体器官移植受者移植物损伤的一种很有前景的非侵入性生物标志物。dd-cfDNA水平升高与排斥反应和移植物损伤密切相关，尤其是抗体介导的排斥反应（ABMR）。虽然供体特异性抗体（dnDSA）在ABMR中至关重要，但dd-cfDNA水平与dnDSA特征（如DSA类别、平均荧光强度（MFI）和HLA靶基因座）之间的关系仍不清楚。
我们分析了75例肾移植受者移植后出现dnDSA的dd-cfDNA水平。根据磁珠反应模式和HLA分型，将dnDSA分为“真”、“可能”或“假”。在一个亚组中，在检测dnDSA和连续随访样本的同时评估dd-cfDNA。
与“可能”和“假”组相比，“真”dnDSA显示出显著更高的dd-cfDNA水平。“假”组中没有dd-cfDNA值超过0.6%，只有一小部分“可能”组的值略高于0.6%。dd-cfDNA水平不受dnDSA靶基因座或数量显著影响。观察到累积dnDSA MFI与dd-cfDNA水平之间存在强相关性，尤其是在具有“真”HLA-DQ定向dnDSA的患者中。连续dd-cfDNA分析显示25%的患者有动态变化，均来自“真”dnDSA组，这些变化往往与累积MFI随时间的变化一致。
这些发现突出了累积dnDSA MFI与dd-cfDNA水平之间的相关性，尤其是在HLA-DQ定向dnDSA中，并表明dnDSA阳性患者的移植物损伤是动态的。对dnDSA和dd-cfDNA的综合监测为评估移植物损伤和同种免疫提供了一种很有前景的非侵入性方法，可能会改善移植后护理。
