Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus
Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus
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DOI：
10.1056/nejmoa2023325
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发表时间：
2020-09-17
影响因子：
158.5
通讯作者：
Alexander, Tobias
中科院分区：
文献类型：
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作者：
Ostendorf, Lennard;Burns, Marie;Alexander, Tobias
达雷妥尤单抗是一种靶向CD38的人单克隆抗体，可耗竭浆细胞，并被批准用于治疗多发性骨髓瘤。长寿命的浆细胞与系统性红斑狼疮的发病机制有关，因为它们分泌自身抗体，但对标准免疫抑制剂无反应。我们描述了达雷妥尤单抗的使用，在两名危及生命的狼疮患者中诱导了大量的临床反应，并通过贝利木单抗（一种B细胞活化因子抗体）维持治疗维持了临床反应。记录了与慢性炎症相关的长寿浆细胞的显著消耗、I型干扰素活性的降低和T细胞转录物的下调。（由德意志研究共同体和其他机构提供支持。表达CD38的长寿浆细胞被认为在系统性红斑狼疮中起致病作用。抗CD38抗体达雷妥尤单抗用于治疗两名患有治疗难治性、危及生命的狼疮并发症的患者，两人的临床症状均得到显著改善。
Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.)Long-lived plasma cells that express CD38 are thought to play a pathogenic role in systemic lupus erythematosus. The anti-CD38 antibody daratumumab was used to treat two patients with treatment-refractory, life-threatening lupus complications, and both had significant clinical improvement.