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一种工具,多重获益:抗 CD38 治疗在抗体介导的排斥反应中的应用

英文原题:One tool, multiple gains: anti-CD38 therapy in antibody-mediated rejection.

查看英文原题

One tool, multiple gains: anti-CD38 therapy in antibody-mediated rejection.

PubMed 2025/09/11(内容时间) Clin Kidney J Q1 · IF 5.3(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

抗体介导的排斥反应(AMR)仍是肾移植中的一大挑战,约占移植物丢失的20%。鉴于传统疗法疗效有限,针对浆细胞的新策略日益受到关注。这些策略包括抗CD38单克隆抗体,如daratumumab、felzartamab和isatuximab。这些药物最初为血液系统恶性肿瘤开发,提供了一种靶向抗体分泌细胞和NK 细胞的新策略,具有降低供者特异性抗体和微血管炎症的潜力。新兴临床数据提示其疗效令人鼓舞且安全性可接受,激发了移植界对其应用的日益浓厚的兴趣。

然而,这些效应似乎是短暂的,个体间变异性大,可能受同种免疫应答建立后B细胞群体异质性的影响。值得注意的是,这些治疗药物也会影响B和T调节细胞,引发了关于免疫平衡及T细胞介导排斥反应风险的重要问题。本综述综合了目前对AMR的认识,介绍了Banff 2022诊断框架的更新,并批判性地评估了抗CD38疗法在AMR中令人振奋的潜力和局限性。随着移植界向精准免疫治疗迈进,抗CD38药物可能有助于重塑肾移植的未来治疗范式——前提是其使用由机制性见解和严格的临床评估所指导。

展开英文摘要原文

Antibody-mediated rejection (AMR) remains a challenge in kidney transplantation, responsible for ≈20% of allograft loss. Given the limited efficiency of conventional therapies, there has been growing interest in new strategies targeting plasma cells. These include anti-CD38 monoclonal antibodies such as daratumumab, felzartamab and isatuximab.

These agents, originally developed for haematologic malignancies, offer a novel strategy to target antibody secreting cells and natural killer cells, with the potential to reduce donor-specific antibodies and microvascular inflammation. Emerging clinical data suggest promising efficacy with an acceptable safety profile, sparking growing interest in their use within the transplant community.

However, these effects appear transient, with a high interindividual variability, likely influenced by the heterogeneity of B cell populations after establishment of an allo-immune response. Of note, these therapeutics also affect B and T regulatory cells, raising important questions about immune balance with the risk of T cell-mediated rejection.

This review synthesizes the current understanding of AMR, presents the Banff 2022 diagnostic frameworks updates and critically appraises the exciting potential and limitations of anti-CD38 therapies in AMR. As the transplant community shifts toward precision immunotherapy, anti-CD38 agents may help reshape future treatment paradigms in kidney transplantation-provided their use is guided by mechanistic insights and rigorous clinical evaluation.

论文信息

作者
Etiève R、Van Wynsberghe M、Grangé S、Laurent C、Lemoine M、Candon S、Bertrand D、de Nattes T
第一作者单位
Nephrology Department, CHU Rouen, Rouen, France.France
通讯作者单位
Nephrology Department, U1234, Univ Rouen Normandy, CIC-CRB 1404, CHU Rouen, Rouen, France.France
期刊
Clinical kidney journal2025 Dec
原文标识
PubMed 41393858 · DOI 10.1093/ckj/sfaf283