Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.
Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.
复制标题
在Chaple疾病中抑制C5的广泛有效的代谢和免疫恢复。
DOI：
10.1038/s41590-020-00830-z
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发表时间：
2021-03
影响因子：
30.5
通讯作者：
Lenardo MJ
中科院分区：
文献类型：
--
作者：
Ozen A;Kasap N;Vujkovic-Cvijin I;Apps R;Cheung F;Karakoc-Aydiner E;Akkelle B;Sari S;Tutar E;Ozcay F;Uygun DK;Islek A;Akgun G;Selcuk M;Sezer OB;Zhang Y;Kutluk G;Topal E;Sayar E;Celikel C;Houwen RHJ;Bingol A;Ogulur I;Eltan SB;Snow AL;Lake C;Fantoni G;Alba C;Sellers B;Chauvin SD;Dalgard CL;Harari O;Ni YG;Wang MD;Devalaraja-Narashimha K;Subramanian P;Ergelen R;Artan R;Guner SN;Dalgic B;Tsang J;Belkaid Y;Ertem D;Baris S;Lenardo MJ
补体过度活化、血管病性血栓形成和蛋白丢失性肠病（CHAPLE病）是由补体调节蛋白CD 55的遗传丢失引起的致死性疾病，其导致补体和先天免疫的过度活化以及由于免疫球蛋白（IG）在肠中消耗而引起的免疫缺陷。我们报告了使用补体C5抑制剂依库珠单抗对CHAPLE患者进行药物治疗所积累的体内人体数据，并观察到胃肠道病理学停止以及正常免疫和代谢恢复。我们发现，患者迅速重新正常化IG浓度和其他血清蛋白，如适体分析所揭示的，重新建立健康的肠道微生物组，停止IG替代和其他治疗，并表现出追赶生长。因此，我们显示依库珠单抗对C5的阻断有效地重新建立了先天免疫补体系统的调节，以基本上减少人类中CD55缺乏的病理生理学表现。
Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55 leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin (Ig) wasting in the intestine. We report in vivo human data that we accumulated using the complement C5 inhibitor eculizumab for the medical treatment of CHAPLE patients and observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized Ig concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued Ig replacement and other treatments, and exhibited catch-up growth. Thus, we show blockade of C5 by eculizumab effectively re-establishes the regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.
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影响因子：
4.6
作者：
Candia J;Cheung F;Kotliarov Y;Fantoni G;Sellers B;Griesman T;Huang J;Stuccio S;Zingone A;Ryan BM;Tsang JS;Biancotto A
通讯作者：
Biancotto A
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
DOI：
10.4049/jimmunol.1402956
发表时间：
2015-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Giles JL;Choy E;van den Berg C;Morgan BP;Harris CL
通讯作者：
Harris CL
影响因子：
4.6
作者：
Ding, H.;Kharboutli, M.;Wu, T.
通讯作者：
Wu, T.
影响因子：
11.5
作者：
Eiseman, Julie L.;Guo, Jianxia;Egorin, Merrill J.
通讯作者：
Egorin, Merrill J.