Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency.
Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency.
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我们报告了一种新的致命的人类遗传性疾病的临床描述和分子解剖，其特征是慢性自身炎症，侵袭性细菌感染和肌支链淀粉病。来自两种激酶的患者携带HOIL 1的双等位基因表达缺失和功能缺失突变，HOIL 1是线性泛素化链组装复合物（LUBAC）的一个组成部分。这些突变导致LUBAC稳定性受损。在患者的成纤维细胞中，响应于白细胞介素-1 β（IL-1β）的NF-κB活化受到损害。相比之下，患者的单核白细胞，特别是单核细胞，对IL-1β反应过度。因此，人HOIL-1和LUBAC缺陷对IL-1β应答的影响在细胞类型之间不同，这与这些患者中自身炎症和免疫缺陷的独特相关性一致。这些数据表明LUBAC在不同细胞类型中不同地调节NF-κ B依赖性IL-1β应答。
We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic auto-inflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1, a component the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin-1β (IL-1β) was compromised in the patients’ fibroblasts. By contrast, the patients’ mononuclear leukocytes, particularly monocytes, were hyperresponsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of auto-inflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1β responses differently in different cell types.
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DOI：
10.1084/jem.20101597
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Byun M;Abhyankar A;Lelarge V;Plancoulaine S;Palanduz A;Telhan L;Boisson B;Picard C;Dewell S;Zhao C;Jouanguy E;Feske S;Abel L;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1056/nejmoa1102140
发表时间：
2012-01-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ombrello MJ;Remmers EF;Sun G;Freeman AF;Datta S;Torabi-Parizi P;Subramanian N;Bunney TD;Baxendale RW;Martins MS;Romberg N;Komarow H;Aksentijevich I;Kim HS;Ho J;Cruse G;Jung MY;Gilfillan AM;Metcalfe DD;Nelson C;O'Brien M;Wisch L;Stone K;Douek DC;Gandhi C;Wanderer AA;Lee H;Nelson SF;Shianna KV;Cirulli ET;Goldstein DB;Long EO;Moir S;Meffre E;Holland SM;Kastner DL;Katan M;Hoffman HM;Milner JD
通讯作者：
Milner JD
DOI：
10.1056/nejmoa0807865
发表时间：
2009-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aksentijevich I;Masters SL;Ferguson PJ;Dancey P;Frenkel J;van Royen-Kerkhoff A;Laxer R;Tedgård U;Cowen EW;Pham TH;Booty M;Estes JD;Sandler NG;Plass N;Stone DL;Turner ML;Hill S;Butman JA;Schneider R;Babyn P;El-Shanti HI;Pope E;Barron K;Bing X;Laurence A;Lee CC;Chapelle D;Clarke GI;Ohson K;Nicholson M;Gadina M;Yang B;Korman BD;Gregersen PK;van Hagen PM;Hak AE;Huizing M;Rahman P;Douek DC;Remmers EF;Kastner DL;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
影响因子：
64.8
作者：
Ikeda, Fumiyo;Deribe, Yonathan Lissanu;Skanland, Sigrid S.;Stieglitz, Benjamin;Grabbe, Caroline;Franz-Wachtel, Mirita;van Wijk, Sjoerd J. L.;Goswami, Panchali;Nagy, Vanja;Terzic, Janos;Tokunaga, Fuminori;Androulidaki, Ariadne;Nakagawa, Tomoko;Pasparakis, Manolis;Iwai, Kazuhiro;Sundberg, John P.;Schaefer, Liliana;Rittinger, Katrin;Macek, Boris;Dikic, Ivan
通讯作者：
Dikic, Ivan
影响因子：
3.7
作者：
Hostager, Bruce S.;Kashiwada, Masaki;Rothman, Paul B.
通讯作者：
Rothman, Paul B.