先天不足和后天免疫IKBKB突变造成的。
文章的细节
-
引用
复制到剪贴板 -
Pannicke U,鲍曼B,福克斯,Henneke P, Rensing-Ehl, Rizzi M,简达,这些K, Schlesier M, Holzmann K, Borte年代,Laux C,臀部EM,罗森博格,他T, Schrezenmeier H, Wirth T, Ehl年代,施罗德ML,施瓦兹K
先天不足和后天免疫IKBKB突变造成的。
郑传经地中海J。2013年12月26日,369(26):2504 - 14所示。doi: 10.1056 / NEJMoa1309199。
- PubMed ID
-
24369075 (在PubMed]
- 文摘
-
背景:重度联合免疫缺陷(SCID)组成的异质群体遗传缺陷的体液和细胞免疫。许多患者SCID lymphocyte-activation缺陷,仍无特征。方法:我们在4名患者进行基因研究,从四个家庭北部的克里族血统,曾SCID的临床特征,包括早期发病严重的病毒,细菌,真菌感染,尽管正常b细胞和t细胞数量。全基因组纯合性映射是用于识别候选区域,发现8号染色体上;这个区间内所有基因测序。免疫细胞数量,在激活信号转导,效应器功能进行了研究。结果:患者低丙球蛋白血症或agammaglobulinemia,其外周血B细胞和T细胞几乎只天真的表现型。调节性T细胞和T细胞gammadelta缺席。所有患者进行纯合子的重复——c。IKBKB 13 1292 dupg外显子,编码IkappaB激酶2 (IKK2,也称为IKKbeta)——IKK2导致损失的表达,一个组件的IKK-nuclear因素kappaB (NF-kappaB)通路。 Immune cells from the patients had impaired responses to stimulation through T-cell receptors, B-cell receptors, toll-like receptors, inflammatory cytokine receptors, and mitogens. CONCLUSIONS: A form of human SCID is characterized by normal lymphocyte development despite a loss of IKK2 function. IKK2 deficiency results in an impaired response to activation stimuli in a variety of immune cells, leading to clinically relevant impairment of adaptive and innate immunity. Although Ikk2 deficiency is lethal in mouse embryos, our observations suggest a more restricted, unique role of IKK2-NF-kappaB signaling in humans. (Funded by the German Federal Ministry of Education and Research and others.).