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Blood：腺苷脱氨酶2缺陷病（DADA2）的发病机制！

2019-04-25 MedSci MedSci原创

腺苷脱氨酶2DADA2腺苷受体巨噬细胞炎症
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腺苷脱氨酶2 (ADA2)基因(以前称为CECR1)的常染色体隐性功能丧失性突变，使ADA2活性降低，导致系统性血管炎，即ADA2缺陷（DADA2）。一直以来，普遍认为中性粒细胞和一种称为低密度粒细胞(LDGs)的中性粒细胞亚群，至少在一定程度上，通过中性粒细胞胞外陷阱(NETs)的形成，在血管炎的发病机制中发挥一定作用。本研究目的是明确中性粒细胞和NETs在DADA2中是否有致病作用。体内研究显

腺苷脱氨酶2 (ADA2)基因(以前称为CECR1)的常染色体隐性功能丧失性突变，使ADA2活性降低，导致系统性血管炎，即ADA2缺陷（DADA2）。一直以来，普遍认为中性粒细胞和一种称为低密度粒细胞(LDGs)的中性粒细胞亚群，至少在一定程度上，通过中性粒细胞胞外陷阱(NETs)的形成，在血管炎的发病机制中发挥一定作用。

本研究目的是明确中性粒细胞和NETs在DADA2中是否有致病作用。

体内研究显示，DADA2患者受累的胃肠道组织中存在NETs和巨噬细胞。在DADA2的活动期，可以观察到大量的循环LDGs倾向自发形成NET，而且经抗TNF治疗诱导缓解后明显减少。在携带单等位基因ADA2突变的未发病的家族成员中也观察到循环LDGs增多。

腺苷通过与A1和A3腺苷受体(ARs)A1和A3结合以活性氧(ROS)和肽基赖氨酸脱亚酶(PAD)依赖性通路，触发NET形成，尤其是在女性患者的中性粒细胞中。重组ADA2、A1/A3 AR拮抗剂或A2A激动剂均可抑制腺苷诱导的NET形成。

用DADA2患者来源的NET培养M1巨噬细胞，TNF-α的分泌量明显增多。用A2AAR激动剂处理可减少NF-kB的核易位及DADA2单核细胞来源的巨噬细胞所产生的炎性细胞因子。

总而言之，本研究结果表明，中性粒细胞可能参与DADA2的发生发展。调节腺苷介导的NET形成或可为DADA2和其他潜在炎性疾病提供一种新的、靶向治疗方法。

原始出处：

Carmelo Carmona-Rivera， et al. Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2. Blood 2019 ：blood.2018892752； doi： https：//doi.org/10.1182/blood.2018892752 

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    2019-06-10 dangious

    #腺苷脱氨酶2#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1810639, encodeId=4afa181063947, content=<a href='/topic/show?id=1b4785e431b' target=_blank style='color:#2F92EE;'>#腺苷脱氨酶2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85743, encryptionId=1b4785e431b, topicName=腺苷脱氨酶2)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ce4238, createdName=dangious, createdTime=Mon Jun 10 05:00:00 CST 2019, time=2019-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784073, encodeId=970a1e8407348, content=<a href='/topic/show?id=07f05661d4' target=_blank style='color:#2F92EE;'>#DADA2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5661, encryptionId=07f05661d4, topicName=DADA2)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6595338, createdName=xuruicheng, createdTime=Thu Dec 26 08:00:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1264696, encodeId=1f2112646966d, content=<a href='/topic/show?id=150f19229c' target=_blank style='color:#2F92EE;'>#ADA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1922, encryptionId=150f19229c, topicName=ADA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Sat Apr 27 13:00:00 CST 2019, time=2019-04-27, status=1, ipAttribution=)]
    2019-12-26 xuruicheng

    #DADA2#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1810639, encodeId=4afa181063947, content=<a href='/topic/show?id=1b4785e431b' target=_blank style='color:#2F92EE;'>#腺苷脱氨酶2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85743, encryptionId=1b4785e431b, topicName=腺苷脱氨酶2)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ce4238, createdName=dangious, createdTime=Mon Jun 10 05:00:00 CST 2019, time=2019-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784073, encodeId=970a1e8407348, content=<a href='/topic/show?id=07f05661d4' target=_blank style='color:#2F92EE;'>#DADA2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5661, encryptionId=07f05661d4, topicName=DADA2)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6595338, createdName=xuruicheng, createdTime=Thu Dec 26 08:00:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1264696, encodeId=1f2112646966d, content=<a href='/topic/show?id=150f19229c' target=_blank style='color:#2F92EE;'>#ADA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1922, encryptionId=150f19229c, topicName=ADA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Sat Apr 27 13:00:00 CST 2019, time=2019-04-27, status=1, ipAttribution=)]
    2019-04-27 般若傻瓜

    #ADA#

    0