Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms.
Germline variants in UNC13D and AP3B1 are enriched in COVID-19 patients experiencing severe cytokine storms.
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UNC13D 和 AP3B1 的种系变异在经历严重细胞因子风暴的 COVID-19 患者中丰富
DOI：
10.1038/s41431-021-00886-x
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Wang QF
中科院分区：
文献类型：
--
作者：
Luo H;Liu D;Liu W;Wang G;Chen L;Cao Y;Wei J;Xiao M;Liu X;Huang G;Wang W;Zhou J;Wang QF
2019年重症冠状病毒病(新冠肺炎)的特点是严重的细胞因子风暴，这是一种与致命后果的发生密切相关的高炎症状态。为什么有些人似乎特别容易受到严重的细胞因子风暴的影响，这一点尚不清楚。原发免疫缺陷(PID)相关基因是一类遗传性因子，可调节宿主对感染的炎症反应，尤其是与噬血细胞淋巴组织细胞增多症(HLH)相关的基因，被认为是过度细胞因子风暴的诱因。我们分析了pID基因变异与新冠肺炎中严重的细胞因子风暴的相关性。我们对233例住院的新冠肺炎患者进行了全外显子组测序，发现在经历严重细胞因子风暴的新冠肺炎患者中，四个PID基因变异体(UNC13D、AP3B1、RNF168、DHX58)显著富含。新冠肺炎患者中两个典型的促黄体生成素基因UN13DorAP3B1变异的总比例在高水平细胞因子组显著高于低水平组(33.3vs.5.7%，P<； 0.001)。UC13D和AP3B1的生殖系变异与严重的细胞因子风暴的发生有关，这是新冠肺炎的致命后果。这些发现促进了对个体对严重细胞因子风暴易感性的理解，并有助于优化新冠肺炎的当前管理。
Critically ill coronavirus disease 2019 (COVID-19) is characterized by severe cytokine storms, a hyperinflammatory condition intimately related to the development of fatal outcomes. Why some individuals seem particularly vulnerable to severe cytokine storms is still unknown. Primary immunodeficiency (PID)-related genes are inherited factors that dysregulate host inflammatory responses to infection, especially hemophagocytic lymphohistiocytosis (HLH)-related genes, established as contributors to the development of excessive cytokine storms. We analyzed the association between PID gene variants with severe cytokine storms in COVID-19. We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D,AP3B1,RNF168,DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants inUNC13DorAP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%,P< 0.001). Germline variants inUNC13DandAP3B1were associated with the development of severe cytokine storms, fatal outcomes in COVID-19. These findings advance the understanding of individual susceptibility to severe cytokine storms and help optimize the current management of COVID-19.
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影响因子：
9.1
作者：
Tangye, Stuart G.;Al-Herz, Waleed;Sullivan, Kathleen E.
通讯作者：
Sullivan, Kathleen E.
影响因子：
9.1
作者：
Bousfiha A;Jeddane L;Picard C;Ailal F;Bobby Gaspar H;Al-Herz W;Chatila T;Crow YJ;Cunningham-Rundles C;Etzioni A;Franco JL;Holland SM;Klein C;Morio T;Ochs HD;Oksenhendler E;Puck J;Tang MLK;Tangye SG;Torgerson TR;Casanova JL;Sullivan KE
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Sullivan KE
DOI：
10.1016/j.jaci.2015.06.048
发表时间：
2016-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
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作者：
Cetica V;Sieni E;Pende D;Danesino C;De Fusco C;Locatelli F;Micalizzi C;Putti MC;Biondi A;Fagioli F;Moretta L;Griffiths GM;Luzzatto L;Aricò M
通讯作者：
Aricò M
影响因子：
14.9
作者：
Song S;Tian D;Li C;Tang B;Dong L;Xiao J;Bao Y;Zhao W;He H;Zhang Z
通讯作者：
Zhang Z
DOI：
10.4049/jimmunol.1501284
发表时间：
2016-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zhang M;Bracaglia C;Prencipe G;Bemrich-Stolz CJ;Beukelman T;Dimmitt RA;Chatham WW;Zhang K;Li H;Walter MR;De Benedetti F;Grom AA;Cron RQ
通讯作者：
Cron RQ