盘点:2019年2月7日Blood研究精选

2019-02-12 zhangfan MedSci原创

2019年2月7日Blood研究精选



【1】封面文章--伤寒沙门氏菌感染血栓形成机制研究


血栓是一种常见的、可危及生命的全身性感染并发症,与多器官损伤相关。研究人员既往发现了一种由鼠伤寒沙门氏菌感染引起的炎症驱动血栓形成的新机制。肝内血栓形成发生在感染消退后的7天内,为单核细胞依赖性的。意料之外的是,虽然脾脏与肝脏有类似的细菌负担,但此时脾脏的血栓并不明显。

近日研究人员发现血栓形成确实在脾脏内发生,但与肝脏相比血流动力学加速明显,特别是在24小时内,随后血栓被迅速分解。血栓形成的独特动力学和细菌负担提供了一种假设的检验,即血栓在健康血管中形成来捕获或清除循环中的细菌,通常称为免疫性血栓。值得注意的是,在感染早期,虽然在被感染的脾脏和肝脏中都可检测到细菌,但组织切片的免疫组化分析显示血栓中仅含有极少量细菌。与此相反,在体外沙门氏菌诱导的血小板聚集物中,可检测到细菌。

【2】Ravulizumab治疗阵发性睡眠性血红蛋白尿


Ravulizumab(ALXN1210),一种新的补体C5抑制剂,可直接完全的维持C5抑制。近日研究人员比较了ravulizumab和依库丽单抗治疗未采用过补体抑制剂治疗的阵发性睡眠性血红蛋白尿(PNH)患者的疗效。

乳酸脱氢酶(LDH)≥1.5倍正常值上限的、至少有一个PNH症状的患者(246位)被随机分至ravulizumab或依库丽单抗组,治疗183天。主要效应结点是不用输血和LDH变正常的患者比例。次要结点是LDH的变化比例、慢性病治疗功能性评估(FACIT)-疲劳评分的变化、突破性溶血的患者比例、血红蛋白稳定和血清游离C5的变化。

根据两个主要结点和所有关键的次要结点,ravulizumab的疗效均非劣于于依库丽单抗:输血避免(73.6% vs 66.1%)、LDH正常化(53.6% vs 49.4%)、LDH的降低比例(-76.8% vs -76.0%)、FACIT-疲劳评分的变化(7.07 vs 6.40)、突破性溶血(4.0% vs 10.7%)。

【3】Ravulizumab替换依库丽单抗治疗阵发性夜间睡眠性血红蛋白尿


Ravulizumab,是一种新的补体C5抑制剂,用于未进行过补体抑制剂治疗的阵发性夜间睡眠性血红蛋白尿(PNH)患者,每8周给药一次,效果不次于每2周用一次依库丽单抗。近日研究人员对ravulizumab相比依库丽单抗应用于临床稳定的PNH患者的疗效进行评估。

195位应用依库丽单抗(900mg/2周)超过6个月的PNH患者被随机分至ravulizumab组(97人)或依库丽单抗组(98人)。主要结点是从起始到第183天时乳酸脱氢酶(LDH)的变化比例。次要结点包括突破性溶血的患者比例、慢性病治疗功能评估(FACIT)-疲劳评分的变化、输血减少和血红蛋白稳定。191位患者完成183天的治疗,ravulizumab治疗的效果非劣于依库丽单,包括LDH的变化比例(差异9.21%)、突破性溶血(5.1)、FACIT-疲劳评分(1.47)、输血减少(5.5)和血红蛋白稳定(1.4)。最常见的副反应是头痛,未发生脑膜炎球菌感染或因不良事件而停药。

【4】HLA配体谱与CML新治疗靶点


白血病免疫在慢性粒细胞白血病(CML)的病程控制和脱离酪氨酸激酶抑制剂(TKI)的缓解状态的维持中起着重要作用。因此抗原特异性免疫疗法有望加强CML的免疫控制,但需要鉴别更多的与CML相关的免疫靶点。

近日研究人员采用基于质谱的方法来识别在原发性CML样品中自然存在的I/II类HLA限制性多肽。利用不同血液学良性样本和深层分子缓解期的CML患者样本的综合数据集进行HLA配体分析比较,描绘出一组新的、常见的、仅在CML中存在的多肽。研究认为,这些非突变的靶抗原具有特异性的相关性,即自然表达缺乏、BCR-ABL-和ABLBCR-来源、HLA限制性多肽,并缺乏已知癌症/睾丸和白血病相关抗原的频繁、肿瘤专属表达。功能性分析显示在CML患者样本中存在自发的抗新鉴定的CML相关肽的T细胞反应,而且其具有在健康志愿者和CML患者样本中诱导产生多功能性和细胞毒性抗原特异性T细胞的能力。

【5】RandaII型单克隆免疫球蛋白沉积病的诊断与治疗


单克隆免疫蛋白沉积病(MIDD)是一种罕见的B细胞克隆疾病的并发症,其特征是单克隆轻链(LCDD)、重链(HCDD)呈刚果红阴性沉积,或两者兼有(LHCDD)。MIDD是一种全身性疾病,肾脏受累明显,肾外表现少见。病理性免疫球蛋白沉积的机制以及与肾脏和患者存活期相关的因素均尚未明确。

研究人员对一个包含255位患者的队列进行回顾性研究。255位患者,其中经活检证实的LCDD有212位(包括单纯性LCDD 154位,合并管型肾病[CN]的LCDD 58位),HCDD 23位,LHCDD 20位。64%的患者表现为肾小球病变,34%的患者表现为有症状的骨髓瘤。LCCD合并CN的患者的表现为急性肾损伤,而其他类型患者表现为慢性肾小球病,其中35%的患者存在肾外症状(大多是肝损和心脏损伤)。在169位进行化疗(58%以硼替佐米为基础)的患者中,67%的患者获得血清游离轻链(FLC)缓解,超过52%的患者获得较好的部分缓解(VGPR)。62位(36%)患者获得肾脏缓解,并全部获得血液学缓解。FLC缓解≥VGPR(OR 4.14)和无严重间质纤维化(OR 3.45)均是肾脏缓解的独立预测因素。

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    2019-02-16 Y—xianghai

    学习了长知识

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    2019-02-16 Y—xianghai

    学习了新知识

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    2019-02-16 Y—xianghai

    学习了长知识

    0

  4. 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    2019-02-16 Y—xianghai

    学习了新知识

    0

  5. 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    2019-02-16 Y—xianghai

    学习了长知识

    0

  6. 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attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Sat Feb 16 16:44:19 CST 2019, time=2019-02-16, status=1, ipAttribution=)]
    2019-02-16 Y—xianghai

    学习了新知识

    0

  7. 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    2019-02-16 Y—xianghai

    学习了长知识

    0

  8. 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    2019-02-16 Y—xianghai

    学习了新知识

    0

  9. 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    2019-02-16 Y—xianghai

    学习了长知识

    0

  10. 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    2019-02-16 Y—xianghai

    学习了新知识

    0

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