Nat Commun:新分子分型推动原发性干燥综合征的精准治疗策略

2021-06-13 xiaozeng MedSci原创

原发性干燥综合征(pSS)是一种慢性的、致残的、复杂的全身性自身免疫疾病,主要影响对象为成年女性,且目前仍缺乏有效的针对性治疗策略。

原发性干燥综合征(pSS)是一种慢性的、致残的、复杂的全身性自身免疫疾病,主要影响对象为成年女性,且目前仍缺乏有效的针对性治疗策略。

尽管唾液腺和泪腺受累是该疾病的一大标志,但在pSS发生发展过程中,可能涉及包括关节、肺、肾脏、肝脏、神经和肌肉骨骼系统等各种器官和系统。因此,该疾病的临床范围从良性缓慢进展的自身免疫性外分泌病到具有显着症状异质性和分散并发症的严重全身性疾病。


pSS的诊断目前主要是基于临床、血清学、组织学和功能参数的组合。此外,五分之一的pSS患者可能出现主要器官受累并伴有潜在的严重终末器官损伤,5%的患者也可能会发展为非霍奇金淋巴瘤。pSS这一自身免疫性疾病被报道由多种环境因素驱动,因此其表现出显著的变异性,且与该疾病的发生、传播和爆发相关。

该疾病的临床表现和病理生理学的异质性也使得该疾病的有效疗法的开发颇具困难。因此,在患者亚组中寻找共同的分子特征可以提高对疾病病因的理解,并促进相关靶向治疗的发展。


在该研究中,研究人员通过一项描述性队列中报告了干燥综合征患者的相关分子分型方案,该方案基于来自300多名欧洲患者队列的全血样本的多组学分析,以及相似数量的年龄和性别匹配的健康的志愿者样本数据。

pSS患者的4组不同典型途径的分子分型

研究人员采用转录组学、基因组学、表观遗传学、细胞因子表达和流式细胞术数据,结合相关临床参数,确定了四个具有不同免疫失调模式的患者亚组(C1-C4)。


C1、C3和C4组患者显示出了IFN通路的病理学相关的高干扰素(IFN)特征,揭示了,且具有各种I型和II型IFN基因富集。与 C3组(中间)和 C4组(较低)相比,C1具有最强的I型和II型基因富集的IFN特征。C4组相比于C3组,具有较强的I型与相当的II型基因富集,而C3组则具有相反的组成。C2组表现出较弱的I型和II型IFN特征。研究人员通过多组学和临床数据进一步的表征了C1、C3和C4组。

不同模块的丰度模式区分四个pSS亚组

总而言之,该研究中识别出的生物标志物可通过机器学习分类器对患者进行亚组分类,从而可在临床试验中重新评估患者对治疗的反应。


原始出处:

Soret, P., Le Dantec, C., Desvaux, E. et al. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome. Nat Commun 12, 3523 (10 June 2021).

 

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    2021-10-03 liye789132251
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    2022-05-27 liuli5079
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  7. 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  8. 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  9. 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likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=25b01886537, createdName=ms1531565637822789, createdTime=Mon Jun 14 13:32:42 CST 2021, time=2021-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973430, encodeId=b0569e3430c3, content=很值得学习 , beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210426/763e7ce2dab140888e41ebc5fca8c4b7/61843205f4d644369d57d751f29054a3.jpg, createdBy=8ba35478954, createdName=ms9000000883963153, createdTime=Mon Jun 14 12:16:19 CST 2021, time=2021-06-14, status=1, ipAttribution=)]
    2021-06-14 ms1531565637822789

    学习了

    0

  10. 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    2021-06-14 ms9000000883963153

    很值得学习

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