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ARD：基因组测序和功能分析确定与系统性红斑狼疮相关MAP4K3/GLK种系和体细胞突变

2021-10-15 MedSci原创 MedSci原创

系统性红斑狼疮
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T细胞中的MAP4K3 (GLK)过表达诱导白细胞介素(IL)-17A产生和自身免疫反应。SLE患者的多个GLK种系和体细胞突变通过增加mRNA或蛋白质稳定性诱导GLK过表达。

     T细胞中的MAP4K3 (GLK)过表达诱导白细胞介素(IL)-17A产生和自身免疫反应。GLK过表达T细胞数量与人系统性红斑狼疮(SLE)的严重程度相关；然而，目前尚不清楚 GLK是如何在SLE患者中上调的。

      来自台湾的研究者在两个独立的来自不同医院/城市的队列中招募了181名SLE患者和250名没有SLE的个体（93名健康对照者和157名SLE患者的家庭成员）。外周血单核细胞的基因组DNA通过下一代测序鉴定GLK基因变异。识别出的GLK种系或体细胞变异通过定点突变和细胞转染，随后通过报告基因检测、质谱、免疫印迹、免疫共沉淀和原位邻近连接实验进行功能研究。

      研究者从1号和2号队列的58名SLE患者中发现在GLK 3'非翻译区(UTR)更高的体细胞变异频率(chr2:39 477 124 A>G)；这些SLE患者的血清抗双链DNA水平升高和血清C3/C4水平降低。3'-UTR的这种体细胞突变增强了T细胞中的GLK mRNA水平。此外，研究者还在1号和2号SLE患者队列中确定了五个具有GLK (A410T) 的种系变异，以及1号队列中另外两名SLE患者的GLK (K650R) 种系变异。在2号队列的一个SLE患者上发现另一个GLK种系变异A579T。两个GLK突变(A410T)和GLK (K650R)抑制由新型E3连接酶makorin环指蛋白4 (MKRN4)诱导的GLK泛素化，使GLK蛋白稳定存在。

结论：

SLE患者的多个GLK种系和体细胞突变通过增加mRNA或蛋白质稳定性诱导GLK过表达。 

 

出处：

Chuang HC, Hung WT, Chen YM, Hsu PM, Yen JH, Lan JL, Tan TH. Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus. Ann Rheum Dis. 2021 Oct 5:annrheumdis-2021-221010. doi: 10.1136/annrheumdis-2021-221010. Epub ahead of print. PMID: 34610951.

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    2021-10-24 ms7514935887898259

    #体细胞突变#

    0

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    2021-12-15 qingrejiedu

    #系统性#

    0

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likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4e492517044, createdName=六月心情, createdTime=Sat Oct 16 15:25:31 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1060971, encodeId=4d4e10609e11a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211204/b697f46076a04a549df4cf2e037f29fa/4d287437091e4aa7b707148db6d4fc52.jpg, createdBy=420a5575209, createdName=付星, createdTime=Sat Oct 16 10:22:53 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
    2022-05-17 lishiwen

    #能分析#

    0

  4. 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topicList=[TopicDto(id=76905, encryptionId=9760e69058c, topicName=系统性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b9b368, createdName=qingrejiedu, createdTime=Wed Dec 15 21:03:24 CST 2021, time=2021-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809977, encodeId=069c18099e7a4, content=<a href='/topic/show?id=2b9d8426121' target=_blank style='color:#2F92EE;'>#能分析#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84261, encryptionId=2b9d8426121, topicName=能分析)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c0050, createdName=lishiwen, createdTime=Tue May 17 10:03:24 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387469, encodeId=8d30138e4699c, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436302, encodeId=283214363023d, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Oct 17 02:03:24 CST 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topicName=null, topicId=null, topicList=[TopicDto(id=26638, encryptionId=c8a526638f6, topicName=体细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1061064, encodeId=27e310610646b, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e7a85637746, createdName=ms1000000430623148, createdTime=Sat Oct 16 15:53:03 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1061054, encodeId=82f1106105479, content=签到, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4e492517044, createdName=六月心情, createdTime=Sat Oct 16 15:25:31 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1060971, encodeId=4d4e10609e11a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211204/b697f46076a04a549df4cf2e037f29fa/4d287437091e4aa7b707148db6d4fc52.jpg, createdBy=420a5575209, createdName=付星, createdTime=Sat Oct 16 10:22:53 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
    2021-10-17 sunrural_42825357

    #狼疮#

    0

  5. 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topicList=[TopicDto(id=76905, encryptionId=9760e69058c, topicName=系统性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b9b368, createdName=qingrejiedu, createdTime=Wed Dec 15 21:03:24 CST 2021, time=2021-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809977, encodeId=069c18099e7a4, content=<a href='/topic/show?id=2b9d8426121' target=_blank style='color:#2F92EE;'>#能分析#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84261, encryptionId=2b9d8426121, topicName=能分析)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c0050, createdName=lishiwen, createdTime=Tue May 17 10:03:24 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387469, encodeId=8d30138e4699c, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436302, encodeId=283214363023d, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Oct 17 02:03:24 CST 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topicName=null, topicId=null, topicList=[TopicDto(id=26638, encryptionId=c8a526638f6, topicName=体细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1061064, encodeId=27e310610646b, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e7a85637746, createdName=ms1000000430623148, createdTime=Sat Oct 16 15:53:03 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1061054, encodeId=82f1106105479, content=签到, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4e492517044, createdName=六月心情, createdTime=Sat Oct 16 15:25:31 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1060971, encodeId=4d4e10609e11a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211204/b697f46076a04a549df4cf2e037f29fa/4d287437091e4aa7b707148db6d4fc52.jpg, createdBy=420a5575209, createdName=付星, createdTime=Sat Oct 16 10:22:53 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
    2021-10-17 zhouqu_8

    #红斑#

    0

  6. 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topicList=[TopicDto(id=76905, encryptionId=9760e69058c, topicName=系统性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2b9b368, createdName=qingrejiedu, createdTime=Wed Dec 15 21:03:24 CST 2021, time=2021-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809977, encodeId=069c18099e7a4, content=<a href='/topic/show?id=2b9d8426121' target=_blank style='color:#2F92EE;'>#能分析#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84261, encryptionId=2b9d8426121, topicName=能分析)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5c0050, createdName=lishiwen, createdTime=Tue May 17 10:03:24 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387469, encodeId=8d30138e4699c, content=<a href='/topic/show?id=8a3a6814425' target=_blank style='color:#2F92EE;'>#狼疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68144, encryptionId=8a3a6814425, topicName=狼疮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7a6e2500005, createdName=sunrural_42825357, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436302, encodeId=283214363023d, content=<a href='/topic/show?id=22f8e71238d' target=_blank style='color:#2F92EE;'>#红斑#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77123, encryptionId=22f8e71238d, topicName=红斑)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438193, encodeId=9358143819369, content=<a href='/topic/show?id=48f9418406e' target=_blank style='color:#2F92EE;'>#基因组测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41840, encryptionId=48f9418406e, topicName=基因组测序)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438360, encodeId=12e9143836044, content=<a href='/topic/show?id=c8a526638f6' target=_blank style='color:#2F92EE;'>#体细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26638, encryptionId=c8a526638f6, topicName=体细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Oct 17 02:03:24 CST 2021, time=2021-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1061064, encodeId=27e310610646b, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e7a85637746, createdName=ms1000000430623148, createdTime=Sat Oct 16 15:53:03 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1061054, encodeId=82f1106105479, content=签到, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4e492517044, createdName=六月心情, createdTime=Sat Oct 16 15:25:31 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1060971, encodeId=4d4e10609e11a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211204/b697f46076a04a549df4cf2e037f29fa/4d287437091e4aa7b707148db6d4fc52.jpg, createdBy=420a5575209, createdName=付星, createdTime=Sat Oct 16 10:22:53 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
    2021-10-17 zhouqu_8

    #基因组测序#

    0

  7. 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likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4e492517044, createdName=六月心情, createdTime=Sat Oct 16 15:25:31 CST 2021, time=2021-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1060971, encodeId=4d4e10609e11a, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211204/b697f46076a04a549df4cf2e037f29fa/4d287437091e4aa7b707148db6d4fc52.jpg, createdBy=420a5575209, createdName=付星, createdTime=Sat Oct 16 10:22:53 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
    2021-10-17 zhouqu_8

    #体细胞#

    0

  8. 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    2021-10-16 ms1000000430623148

    学习了

    0

  9. 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    2021-10-16 六月心情

    签到

    0

  10. 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    2021-10-16 付星

    学习了

    0

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