A&R:尿液蛋白质组学和肾脏单细胞转录组学提示白细胞介素16在狼疮肾炎中的作用

2022-05-19 MedSci原创 MedSci原创

与没有系统性红斑狼疮的对照组相比,该研究确定了237个与狼疮性肾炎相关的尿液生物标志物。白细胞介素16 (IL-16)、CD163和转化生长因子β反映了肾内肾炎的活性。

   目的:目前狼疮性肾炎(LN)治疗仅对30%的患者有效,因此需要新的治疗策略。该研究团队进行了这项研究,以通过分析接受治疗的LN患者的纵向尿液蛋白质组学特征来提出新的机制假设并探索新的生物标志物。

   方法:研究人员在诊断性肾活检时以及3612个月后量化了30LN患者的 1000种尿蛋白。然后根据基线临床特征和纵向轨迹分析在尿液蛋白质组中检测到的蛋白质和分子途径。使用来自LN患者的肾活检切片的单细胞转录组学评估候选生物标志物的肾内表达。

   结果:尿液蛋白质组学分析揭示了多种生物学通路,包括趋化性、中性粒细胞活化、血小板脱粒和细胞外基质组织,这些通路都可以无创性地在尿液中进行量化和监测。与没有系统性红斑狼疮的对照组相比,该研究确定了237个与LN相关的尿液生物标志物。白细胞介素16 (IL-16)CD163和转化生长因子β反映了肾内肾炎的活性。对治疗的反应与尿液中IL-16的减少平行,IL16是一种具有促炎和趋化特性的CD4配体。单细胞 RNA测序独立证明IL16LN肾脏中大多数浸润性免疫细胞表达的第二大细胞因子。在肾损伤的关键部位发现了产生IL-16的细胞。

   结论:尿液蛋白质组学可通过无创监测活跃的肾内生物通路,从而显著改变LN的诊断和治疗。这些发现表明IL-16LN发病机制中的作用,将其指定为潜在的可治疗靶标和生物标志物。

 

出处:Fava, A., Rao, D.A., Mohan, C., Zhang, T., Rosenberg, A., Fenaroli, P., Belmont, H.M., Izmirly, P., Clancy, R., Trujillo, J.M., Fine, D., Arazi, A., Berthier, C.C., Davidson, A., James, J.A., Diamond, B., Hacohen, N., Wofsy, D., Raychaudhuri, S., Apruzzese, W., , Buyon, J. and Petri, M. (2022), Urine Proteomics and Renal Single-Cell Transcriptomics Implicate Interleukin-16 in Lupus Nephritis. Arthritis Rheumatol, 74: 829-839. https://doi.org/10.1002/art.42023

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    2023-03-09 mjldent
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  5. 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    2022-05-21 2022.4

    每日学习了

    0

  6. 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target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Fri May 20 23:11:06 CST 2022, time=2022-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332958, encodeId=05dd1332958ce, content=<a href='/topic/show?id=d17c68153ab' target=_blank style='color:#2F92EE;'>#狼疮肾炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68153, encryptionId=d17c68153ab, topicName=狼疮肾炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4902500082, createdName=1249883fm12暂无昵称, createdTime=Fri May 20 23:11:06 CST 2022, time=2022-05-20, status=1, ipAttribution=), 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  7. 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  8. 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  9. 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  10. 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