Clinical and Immunological Features of Human BCL10 Deficiency.
Clinical and Immunological Features of Human BCL10 Deficiency.
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DOI：
10.3389/fimmu.2021.786572
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发表时间：
2021
影响因子：
7.3
通讯作者：
Pérez de Diego R
中科院分区：
文献类型：
--
作者：
Garcia-Solis B;Van Den Rym A;Pérez-Caraballo JJ;Al-Ayoubi A;Alazami AM;Lorenzo L;Cubillos-Zapata C;López-Collazo E;Pérez-Martínez A;Allende LM;Markle J;Fernández-Arquero M;Sánchez-Ramón S;Recio MJ;Casanova JL;Mohammed R;Martinez-Barricarte R;Pérez de Diego R
CARD-Bcl10-MALT1(CBM)复合体对人体免疫反应的正确组装至关重要。其某些成分如CARD9、CARD11和MALT1缺陷的临床和免疫学后果已被详细阐明。然而，Bcl10缺陷患者的稀缺阻碍了对这种遗传病的详细了解。到目前为止，只有两名Bcl10缺乏症患者被报告。在此，我们对另一例常染色体隐性遗传性完全Bcl10缺乏症患者进行了深入的描述，该患者是由导致表达缺失的无义突变引起的(K63X)。结合非监督聚类和机器学习计算方法，我们获得了Bcl10缺乏在不同白细胞群体中的后果的彻底表征。我们发现，除了先前报道的几乎没有记忆B细胞和T细胞外，该患者还表现出NK、γδT、Tregs和TFH细胞的减少。患者自幼起反复呼吸道感染，并有致命性严重传染病家族史。幸运的是，造血干细胞移植(HSCT)治愈了她。总体而言，这份报告强调了早期基因诊断对治疗Bcl10缺陷患者的重要性，并将造血干细胞移植作为治愈这种疾病的推荐治疗方法。
The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and TFH cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.
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DOI：
10.1056/nejmoa1208487
发表时间：
2013-10-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Lanternier F;Pathan S;Vincent QB;Liu L;Cypowyj S;Prando C;Migaud M;Taibi L;Ammar-Khodja A;Stambouli OB;Guellil B;Jacobs F;Goffard JC;Schepers K;Del Marmol V;Boussofara L;Denguezli M;Larif M;Bachelez H;Michel L;Lefranc G;Hay R;Jouvion G;Chretien F;Fraitag S;Bougnoux ME;Boudia M;Abel L;Lortholary O;Casanova JL;Picard C;Grimbacher B;Puel A
通讯作者：
Puel A
影响因子：
6.7
作者：
Gringhuis SI;Wevers BA;Kaptein TM;van Capel TM;Theelen B;Boekhout T;de Jong EC;Geijtenbeek TB
通讯作者：
Geijtenbeek TB
影响因子：
7.3
作者：
Lu HY;Bauman BM;Arjunaraja S;Dorjbal B;Milner JD;Snow AL;Turvey SE
通讯作者：
Turvey SE
影响因子：
7.3
作者：
De Bruyne M;Hoste L;Bogaert DJ;Van den Bossche L;Tavernier SJ;Parthoens E;Migaud M;Konopnicki D;Yombi JC;Lambrecht BN;van Daele S;Alves de Medeiros AK;Brochez L;Beyaert R;De Baere E;Puel A;Casanova JL;Goffard JC;Savvides SN;Haerynck F;Staal J;Dullaers M
通讯作者：
Dullaers M
影响因子：
9.1
作者：
Arango-Franco, Carlos A.;Moncada-Velez, Marcela;Luis Franco, Jose
通讯作者：
Luis Franco, Jose