Department of Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Berlin Institute of Health, Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany.
Transpl Int. 2024 Aug 1;37:13213. doi: 10.3389/ti.2024.13213. eCollection 2024.
Antibody-mediated rejection (AMR) is among the most frequent causes for graft loss after kidney transplantation. While there are no approved therapies, several case reports with daratumumab and the very recent phase 2 trial of felzartamab in AMR have indicated the potential efficacy of therapeutic interventions targeting CD38. Donor-derived cell-free DNA (dd-cfDNA) is an emerging biomarker with injury-specific release and a short half-life, which could facilitate early diagnosis of AMR and monitoring of treatment response. We describe two cases of patients with chronic active AMR, who were treated with monthly daratumumab infusions, and in whom donor-derived cell-free DNA (dd-cfDNA) was measured longitudinally to monitor treatment response. In both patients, daratumumab treatment led to stabilization of kidney function parameters, a strong decline of dd-cfDNA below the previously established threshold for rejection, and partial or complete histologic resolution of AMR activity. Our case series suggests that dd-cfDNA may be a useful companion biomarker for longitudinal monitoring of anti-CD38 treatment in patients with AMR.
抗体介导的排斥反应（AMR）是肾移植后移植物丢失的最常见原因之一。虽然目前尚无批准的治疗方法，但已有几例使用达雷妥尤单抗和最近针对 AMR 的 felzartamab 的 2 期试验的个案报告表明，针对 CD38 的治疗干预具有潜在疗效。供体来源的无细胞 DNA（dd-cfDNA）是一种新兴的生物标志物，具有损伤特异性释放和较短的半衰期，可促进 AMR 的早期诊断和治疗反应的监测。我们描述了两例接受每月达雷妥尤单抗输注治疗的慢性活动性 AMR 患者的情况，并对供体来源的无细胞 DNA（dd-cfDNA）进行了纵向测量，以监测治疗反应。在这两例患者中，达雷妥尤单抗治疗导致肾功能参数稳定，dd-cfDNA 强烈下降至先前建立的排斥阈值以下，并且 AMR 活动的部分或完全组织学缓解。我们的病例系列表明，dd-cfDNA 可能是 AMR 患者接受抗-CD38 治疗纵向监测的有用伴随生物标志物。
