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Blood:抑制补体C1s可显著缓解冷凝集素病患者的溶血性贫血

2019-01-08 MedSci MedSci原创

冷凝集素病是一种难以治疗的自身免疫性溶血性贫血,其免疫球蛋白M抗体与红细胞结合并固定补体,主要表现为血管外溶血。抗C1s抗体sutimlimab(苏替莫单抗)是否可缓解溶血性贫血?Ulrich Jager等人开展了一Ib期临床试验,招募了10位冷凝集素病患者,予以10 mg/kg苏替莫单抗的测试剂量,随后1-4天予以60 mg/kg的全剂量,并额外用药3周(60 mg/kg·周)。无药物相关的严重

冷凝集素病是一种难以治疗的自身免疫性溶血性贫血,其免疫球蛋白M抗体与红细胞结合并固定补体,主要表现为血管外溶血。

抗C1s抗体sutimlimab(苏替莫单抗)是否可缓解溶血性贫血?Ulrich Jager等人开展了一Ib期临床试验,招募了10位冷凝集素病患者,予以10 mg/kg苏替莫单抗的测试剂量,随后1-4天予以60 mg/kg的全剂量,并额外用药3周(60 mg/kg·周)。

无药物相关的严重副反应。7位患者病情缓解,血红蛋白增加>2g/dL。苏替莫单抗第1周内即可迅速将血红蛋白水平升高1.6g/dL(中位值),6周内即可升高3.9g/dL(四分位数范围1.3-4.5;95%CI,2.1-4.5,p=0.005)。对于大部分患者,苏替莫单抗可在24小时内迅速消除血管外溶血,将胆红素水平恢复至正常,并且有4位患者的血红蛋白在1周内恢复正常。停药后3-4周血液中药物水平清除后,溶血性贫血复发。在一个指定的病人项目中,再次采用苏替莫单抗治疗可再现对溶血性贫血的控制。6位既往有输血的患者在治疗期间均无输血需要。

总而言之,苏替莫单抗可迅速阻止冷凝集素病患者C1s补体介导的溶血,显著升高血红蛋白水平,排除输血的需要,而且安全、耐受性良好。


原始出处:

Ulrich Jager,et al.Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease: a first-in-human trial. Blood 2018 :blood-2018-06-856930; doi: https://doi.org/10.1182/blood-2018-06-856930 

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冷凝集素病(Cold agglutinin disease)是一种极度罕见的自身免疫性疾病,特征为循环中的抗体作用于红细胞,引起溶血。症状包括雷诺现象,肢端发绀和溶血性贫血。

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