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CELL：对儿童新冠患者的多系统炎症综合征的免疫学研究

2020-12-22 向日葵医学社 MedSci原创

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导语：研究人员在CELL杂志发文，其对健康儿童、COVID-19之前入组的川崎病儿童、SARS-CoV-2感染儿童和出现MIS-C的儿童的血液免疫细胞、细胞因子和自身抗体进行系统性分析。

导语：研究人员在CELL杂志发文，其对健康儿童、COVID-19之前入组的川崎病儿童、SARS-CoV-2感染儿童和出现MIS-C的儿童的血液免疫细胞、细胞因子和自身抗体进行系统性分析。

　　严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2），最早于2019年12月在武汉出现，随后在2020年2月初迅速蔓延至多个国家，尤其是欧洲和意大利北部地区。

　　来自中国的首批报告显示，与感染SARS-CoV-2的成人相比，儿童出现的症状较轻。这背后的原因尚未确定，但有几种理论被讨论过，涉及免疫系统的差异，如胸腺功能、对普通感冒冠状病毒的交叉反应性免疫，病毒进入受体ACE2表达的差异，以及儿童与老年人相比整体健康状况较好等。

　　儿童轻度COVID-19在意大利北部等疾病高发地区也得到了证实。但是，儿童COVID-19病程总是轻度的观点现在受到挑战，最近在英国、意大利、西班牙和纽约市有儿童出现罕见但非常严重的高炎症综合征的报道。在这些病例系列中，患儿表现为高烧，以及一系列与川崎病相关的症状，如结膜炎、淋巴结病、粘膜皮疹和冠状动脉扩张，最严重的病例还出现心血管休克、脑炎和多器官衰竭。

　　川崎病是一种影响中等大小动脉的血管炎，5岁以下儿童发病率最高，在链球菌感染治疗普遍、风湿热罕见的发达国家，川崎病是获得性心脏病的主要原因。川崎病在具有东亚血统的儿童中发病率特别高，最早在日本被描述。

　　川崎病病理生理学的主流理论涉及到在对病毒感染的急性免疫反应中产生自身反应性抗体，可能在黏膜表面，并集中在产生IgA的浆细胞周围。在川崎病儿童的标本中也发现了动脉壁内的此类细胞。中性粒细胞浸润动脉壁，形成坏死性动脉炎，导致结缔组织的破坏以及动脉扩张。界定川崎病发病机制的努力也揭示了在该病的急性期，产生IL-17的T细胞和调节性T细胞的不平衡。

　　鉴于与COVID-19相关的儿童多系统炎症综合征(MIS-C)的严重性，以及正在进行的流行病发展的不确定性，我们迫切需要了解MIS-C的发病机制、与川崎病的异同，从而制定最佳的治疗策略。

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　　最近，研究人员在CELL杂志发文，其对健康儿童、COVID-19之前入组的川崎病儿童、SARS-CoV-2感染儿童和出现MIS-C的儿童的血液免疫细胞、细胞因子和自身抗体进行系统性分析。研究人员在意大利罗马招募了41名急性SARS-CoV-2感染的儿童，他们的病情都很轻，其将这些儿童称为CoV-2+儿童。研究人员还在罗马招募了3名出现MIS-C的儿童，在瑞典斯德哥尔摩招募了10名出现MIS-C的儿童。研究人员将这些儿童与COVID-19大流行前出现川崎病的28名儿童进行了比较。

图片

　　在成人和老年人中，导致COVID-19重症和死亡的主要原因是免疫激活、过度炎症和免疫病理不受控制。但是分析之后，研究人员发现，MIS-C和川崎病炎症状态有部分重叠，且两者均与成人急性COVID-19高发炎症有差异。

 
　　为了更好地了解MIS-C和川崎病的过度炎症，研究人员通过流式细胞仪评估了外周血单核细胞（PBMC）表型。其发现由CD45RO和CD27的表达定义的CD4+T细胞亚群的分布，以及表达趋化因子受体CXCR5的T-滤泡辅助细胞（TFH）的频率存在差异。

　　为了进一步研究MIS-C和川崎病患者的高炎症免疫状态，研究人员对11名MIS-C患儿和28名川崎病患儿的血浆样本进行了Olink检测。研究人员发现，健康儿童，和感染SARS-CoV-2但没有MIS-C的儿童，大部分是重合的，说明这些CoV-2+的儿童有轻度感染和低度炎症反应。此外，MIS-C的高炎症状态与川崎病不同。在MIS-C患者中，对于川崎病十分重要的IL17A显著降低，表明两者之间免疫病学的差异。

　　总之，研究人员发现，MIS-C的炎症反应不同于严重的急性COVID-19的细胞因子风暴，与川崎病有几个共同的特征，但在T细胞亚群、IL-17A和与动脉损伤相关的生物标志物方面也与川崎病不同。自身抗体剖析提示多种自身抗体可能参与MIS-C的发病机制。

评论区 (6)
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  1. [GetPortalCommentsPageByObjectIdResponse(id=1889441, encodeId=7980188944162, content=<a href='/topic/show?id=f9fa290030a' target=_blank style='color:#2F92EE;'>#免疫学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29003, encryptionId=f9fa290030a, topicName=免疫学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Mon Oct 18 12:20:46 CST 2021, time=2021-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1906540, encodeId=d23e190654045, content=<a href='/topic/show?id=317e5805e9d' target=_blank style='color:#2F92EE;'>#新冠患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58057, encryptionId=317e5805e9d, topicName=新冠患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b3e9205, createdName=tidiq, createdTime=Wed Aug 11 13:20:46 CST 2021, time=2021-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872097, encodeId=e70718e209784, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun May 16 11:20:46 CST 2021, time=2021-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962399, encodeId=5413196239902, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Apr 29 16:20:46 CST 2021, time=2021-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431986, encodeId=c50e1431986bd, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Dec 24 05:20:46 CST 2020, time=2020-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028909, encodeId=45aa102890991, content=新冠肺炎，疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Tue Dec 22 17:20:46 CST 2020, time=2020-12-22, status=1, ipAttribution=)]
    2021-10-18 xiaoyeshuang

    #免疫学#

    0

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    2021-08-11 tidiq

    #新冠患者#

    0

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    2021-05-16 zhaozhouchifen

    #Cell#

    0

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    2021-04-29 维他命

    #CEL#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1889441, encodeId=7980188944162, content=<a href='/topic/show?id=f9fa290030a' target=_blank style='color:#2F92EE;'>#免疫学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29003, encryptionId=f9fa290030a, topicName=免疫学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Mon Oct 18 12:20:46 CST 2021, time=2021-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1906540, encodeId=d23e190654045, content=<a href='/topic/show?id=317e5805e9d' target=_blank style='color:#2F92EE;'>#新冠患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58057, encryptionId=317e5805e9d, topicName=新冠患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b3e9205, createdName=tidiq, createdTime=Wed Aug 11 13:20:46 CST 2021, time=2021-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872097, encodeId=e70718e209784, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun May 16 11:20:46 CST 2021, time=2021-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962399, encodeId=5413196239902, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Apr 29 16:20:46 CST 2021, time=2021-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431986, encodeId=c50e1431986bd, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Dec 24 05:20:46 CST 2020, time=2020-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028909, encodeId=45aa102890991, content=新冠肺炎，疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Tue Dec 22 17:20:46 CST 2020, time=2020-12-22, status=1, ipAttribution=)]
    2020-12-24 zhouqu_8

    #综合征#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1889441, encodeId=7980188944162, content=<a href='/topic/show?id=f9fa290030a' target=_blank style='color:#2F92EE;'>#免疫学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29003, encryptionId=f9fa290030a, topicName=免疫学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Mon Oct 18 12:20:46 CST 2021, time=2021-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1906540, encodeId=d23e190654045, content=<a href='/topic/show?id=317e5805e9d' target=_blank style='color:#2F92EE;'>#新冠患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58057, encryptionId=317e5805e9d, topicName=新冠患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b3e9205, createdName=tidiq, createdTime=Wed Aug 11 13:20:46 CST 2021, time=2021-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872097, encodeId=e70718e209784, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun May 16 11:20:46 CST 2021, time=2021-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962399, encodeId=5413196239902, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Apr 29 16:20:46 CST 2021, time=2021-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431986, encodeId=c50e1431986bd, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Dec 24 05:20:46 CST 2020, time=2020-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028909, encodeId=45aa102890991, content=新冠肺炎，疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Tue Dec 22 17:20:46 CST 2020, time=2020-12-22, status=1, ipAttribution=)]
    2020-12-22 公卫新人

    新冠肺炎，疫情何时才能消失

    0