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Arthritis & Rheumatology：首次描述由于体细胞NLRC4嵌合体引起的迟发性自身炎症性疾病

2021-10-28 MedSci原创 MedSci原创

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本研究旨在描述一名迟发性未表征自身免疫病患者的潜在病因。

    自身炎症性疾病 (AID) 是先天免疫的遗传性疾病，通常始于儿童时期。然而，最近几项研究报告发现越来越多的成年人开始患AID。本研究旨在描述一名迟发性未表征AID 患者的潜在病因。

    方法：使用Sanger测序和下一代测序(NGS)方法进行遗传学研究。计算机结构建模使用 Uniprot数据库中的NLRC4蛋白和不同程序进行（MODELER、Chimera、Prosa2003 和 SPserver）。NLRC4-炎症小体的功能研究采用突变型和野生型NLRC4基因在体外转染细胞，和该患者、健康对照和携带p.Ala439Thr NLRP3变异冷吡啉相关周期性综合征患者的新鲜血液样本。Luminex免疫分析测量循环细胞因子。

     结果：来自西班牙的研究者研究了一名57岁的女性，她在47岁时开始出现反复发作的发热、肌痛、关节痛、弥漫性腹痛、腹泻、腺病和全身炎症，使用抗IL-1药物对这些症状的控制相对较好。NGS分析未检测到任何已知AID相关基因中的种系变异，但在全血中鉴定出p.Ser171Phe NLRC4变异，其等位基因分数(2-4%)与基因嵌合体相容。结构模型分析表明，这种错义变异可能有利于NLRC4蛋白的开放、活性构象，体外和离体实验证实了其寡聚化和激活NLRC4-炎症小体的趋势，随之导致IL-18过量生成。

     结论：研究者已将合子后p.Ser171Phe NLRC4变异体确定为入院患者病情的合理原因。功能和结构研究首次明确支持该突变的获得性功能特征与先前报道的NLRC4致病突变一致。在对成年期开始的无特征AID患者进行诊断性检查时，应考虑这些新证据。

 

出处：

Ionescu D, Peñín-Franch A, Mensa-Vilaró A, Castillo P, Hurtado-Navarro L, Molina-López C, Romero-Chala S, Plaza S, Fabregat V, Buján S, Marques J, Casals F, Yagüe J, Oliva B, Fernández-Pereira LM, Pelegrín P, Aróstegui JI. First Description of Late-Onset Autoinflammatory Disease Due to Somatic NLRC4 Mosaicism. Arthritis Rheumatol. 2021 Oct 20. doi: 10.1002/art.41999. Epub ahead of print. PMID: 34672126.

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    2022-04-20 ms9651749636653578

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topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438362, encodeId=119114383626a, 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=34, 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=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=)]
    2022-06-19 ms6390871039024434

    #Arthritis#

    0

  4. 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style='color:#2F92EE;'>#迟发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94588, encryptionId=45eb94588cd, topicName=迟发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f14236, createdName=经常头晕, createdTime=Tue Mar 08 14:22:23 CST 2022, time=2022-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079641, encodeId=53cf20e964135, content=<a href='/topic/show?id=ec074e823ea' target=_blank style='color:#2F92EE;'>#嵌合体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47823, encryptionId=ec074e823ea, topicName=嵌合体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Thu Mar 10 09:22:23 CST 2022, time=2022-03-10, status=1, ipAttribution=), 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topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438362, encodeId=119114383626a, 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=34, 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=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=)]
    2022-03-08 经常头晕

    #迟发性#

    0

  5. 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style='color:#2F92EE;'>#迟发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94588, encryptionId=45eb94588cd, topicName=迟发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f14236, createdName=经常头晕, createdTime=Tue Mar 08 14:22:23 CST 2022, time=2022-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079641, encodeId=53cf20e964135, content=<a href='/topic/show?id=ec074e823ea' target=_blank style='color:#2F92EE;'>#嵌合体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47823, encryptionId=ec074e823ea, topicName=嵌合体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Thu Mar 10 09:22:23 CST 2022, time=2022-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055462, encodeId=0a0c2055462e5, content=<a href='/topic/show?id=0ad78636442' target=_blank style='color:#2F92EE;'>#自身炎症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86364, encryptionId=0ad78636442, topicName=自身炎症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93e223, createdName=bluefate121, createdTime=Fri Feb 11 02:22:23 CST 2022, time=2022-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055158, encodeId=40d92055158f7, content=<a href='/topic/show?id=c08c8636548' target=_blank style='color:#2F92EE;'>#自身炎症性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86365, encryptionId=c08c8636548, topicName=自身炎症性疾病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b3ad2500191, createdName=12498dd9m11暂无昵称, createdTime=Mon Feb 21 01:22:23 CST 2022, time=2022-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1357817, encodeId=b1ef135e81709, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407768, encodeId=ac77140e7688a, content=<a href='/topic/show?id=a22412862b3' target=_blank style='color:#2F92EE;'>#NLR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438362, encodeId=119114383626a, 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=34, 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=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=)]
    2022-03-10 millore

    #嵌合体#

    0

  6. 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style='color:#2F92EE;'>#迟发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94588, encryptionId=45eb94588cd, topicName=迟发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f14236, createdName=经常头晕, createdTime=Tue Mar 08 14:22:23 CST 2022, time=2022-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079641, encodeId=53cf20e964135, content=<a href='/topic/show?id=ec074e823ea' target=_blank style='color:#2F92EE;'>#嵌合体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47823, encryptionId=ec074e823ea, topicName=嵌合体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Thu Mar 10 09:22:23 CST 2022, time=2022-03-10, status=1, ipAttribution=), 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createdBy=b3ad2500191, createdName=12498dd9m11暂无昵称, createdTime=Mon Feb 21 01:22:23 CST 2022, time=2022-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1357817, encodeId=b1ef135e81709, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407768, encodeId=ac77140e7688a, content=<a href='/topic/show?id=a22412862b3' target=_blank style='color:#2F92EE;'>#NLR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438362, encodeId=119114383626a, 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=34, 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=Fri Oct 29 03:22:23 CST 2021, time=2021-10-29, status=1, ipAttribution=)]
    2022-02-11 bluefate121

    #自身炎症#

    0

  7. 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    2022-02-21 12498dd9m11暂无昵称

    #自身炎症性疾病#

    0

  8. 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    2021-10-29 仁者大医

    #ART#

    0

  9. 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    2021-10-29 yuandd

    #NLR#

    0

  10. 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    2021-10-29 zhouqu_8

    #体细胞#

    0

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