Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity
Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity
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患有进行性免疫缺陷和自身免疫的家族中的 CARD10 突变
DOI：
10.1038/s41423-020-0423-x
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发表时间：
2020
影响因子：
24.1
通讯作者：
Luo Hong
中科院分区：
文献类型：
--
作者：
Yang Dan-hui;Guo Ting;Yuan Zhuang-zhuang;Lei Cheng;Ding Shui-zi;Yang Yi-feng;Tan Zhi-ping;Luo Hong
自身免疫和免疫缺陷以前被认为是相互排斥的条件。然而，随着对复杂的免疫调节系统和信号传导机制的了解的增加，加上遗传分析的应用，已经证明了这两种疾病之间的复杂关系。1近年来，发现了几种轻度的原发性免疫缺陷，表现为与晚期自身免疫和/或过敏重叠的机会性感染。1含半胱天冬酶募集结构域（CARD）的蛋白质CARD 9、CARD 10（CARMA 3）、CARD 11（CARMA 1）和CARD 14（CARMA 2）是膜相关鸟苷酸激酶家族的成员。这些蛋白质通过与B细胞淋巴瘤蛋白10（BCL 10）和粘膜相关淋巴组织淋巴瘤易位基因1（MALT 1）形成细胞内复合物而发挥分子支架的功能，所述复合物对于几种信号传导途径的激活是关键的，所述信号传导途径例如B细胞中κ轻链基因附近的核因子结合（NF-κB）、c-Jun N末端激酶和雷帕霉素途径的哺乳动物靶标，在适应性免疫中。此外，CARD 9、CARD 11和CARD 14基因中的显性或隐性突变已被确定为在患者和家族中存在/不存在自身免疫性疾病和肿瘤的情况下免疫缺陷的遗传原因。4-6
Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions. However, an increased understanding of the complex immune regulatory systems and signaling mechanisms, coupled with the application of genetic analysis, has demonstrated the complex relationships between the two kinds of diseases. 1 In recent years, several mild forms of primary immunodeficiencies have been discovered, presenting with opportunistic infections overlapping autoimmunity and/or allergy late in life. 1Caspase recruitment domain (CARD)-containing proteins, CARD9, CARD10 (CARMA3), CARD11 (CARMA1), and CARD14 (CARMA2), are members of the membrane-associated guanylate kinase family. These proteins function as molecular scaffolds by forming an intracellular complex with B-cell lymphoma protein 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1), which are critical for the activation of several signaling pathways, such as the nuclear factor binding near the κ light chain gene in B cells (NF-κB), c-Jun N-terminal kinase, and mammalian target of rapamycin pathways, during adaptive immunity. 2, 3 In addition, dominant or recessive mutations in the CARD9, CARD11, and CARD14 genes have been identified as genetic causes of immunodeficiencies in the presence/absence of autoimmune diseases and tumors in patients and families. 4-6