Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency.
Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency.
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DOI：
10.1084/jem.20160849
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Pan-Hammarström Q
中科院分区：
文献类型：
--
作者：
Abolhassani H;Edwards ES;Ikinciogullari A;Jing H;Borte S;Buggert M;Du L;Matsuda-Lennikov M;Romano R;Caridha R;Bade S;Zhang Y;Frederiksen J;Fang M;Bal SK;Haskologlu S;Dogu F;Tacyildiz N;Matthews HF;McElwee JJ;Gostick E;Price DA;Palendira U;Aghamohammadi A;Boisson B;Rezaei N;Karlsson AC;Lenardo MJ;Casanova JL;Hammarström L;Tangye SG;Su HC;Pan-Hammarström Q
Abolhassani等人。表明CD70缺陷是一种新的免疫缺陷和EB病毒相关疾病的原因，这让人想起CD27缺陷。CD70-CD27相互作用在调节人体体液免疫和细胞免疫中发挥着不可替代的作用，特别是在控制EBV方面。在这项研究中，我们描述了来自两个不同种族的无血缘关系的家庭的四名患者，他们的主要表现是对EB病毒(EBV)相关疾病的易感性。三名患者出现EBV相关霍奇金淋巴瘤和低丙种球蛋白血症；一名患者还伴有严重的水痘感染。第四名婴儿在婴儿期患有病毒性脑炎。在这些患者中，CD70的纯合移码或框内缺失取消了CD70的表面表达或与其同源受体CD27的结合。外周血淋巴细胞数量正常，但记忆性B细胞和EBV特异性效应记忆性CD8+T细胞比例降低。此外，尽管T细胞增殖正常，但由于CD70缺乏，体外产生的EBV特异性细胞毒T细胞活性降低。这反映了EBV转化的B细胞的激活受损，而不是在杀伤过程中的影响。值得注意的是，CD70缺陷个体的记忆CD8+T细胞上参与控制EBV感染的受体2B4和NKG2D的表达减少，这与它们对EBV感染细胞的杀伤作用减弱一致。因此，常染色体隐性遗传CD70缺陷是一种新的联合免疫缺陷和EBV相关疾病的原因，使人想起遗传性CD27缺陷。总体而言，人类CD70-CD27相互作用因此在T和B细胞介导的免疫中发挥了非多余的作用，特别是在预防EBV和体液免疫方面。
Abolhassani et al. show that CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of CD27 deficiency. CD70–CD27 interactions play a nonredundant role regulating humoral- and cell-mediated immunity in humans, especially for control of EBV. In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)–related diseases. Three patients presented with EBV-associated Hodgkin’s lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal, but the proportions of memory B cells and EBV-specific effector memory CD8+ T cells were reduced. Furthermore, although T cell proliferation was normal, in vitro–generated EBV-specific cytotoxic T cell activity was reduced because of CD70 deficiency. This reflected impaired activation by, rather than effects during killing of, EBV-transformed B cells. Notably, expression of 2B4 and NKG2D, receptors implicated in controlling EBV infection, on memory CD8+ T cells from CD70-deficient individuals was reduced, consistent with their impaired killing of EBV-infected cells. Thus, autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70–CD27 interactions therefore play a nonredundant role in T and B cell–mediated immunity, especially for protection against EBV and humoral immunity.
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影响因子：
15.3
作者：
Hendricks, J;Xiao, YL;Borst, J
通讯作者：
Borst, J
影响因子：
168.9
作者：
CINQUE, P;BRYTTING, M;LINDE, A
通讯作者：
LINDE, A
影响因子：
5.4
作者：
AGEMATSU, K;KOBATA, T;KOMIYAMA, A
通讯作者：
KOMIYAMA, A
影响因子：
64.5
作者：
GOODWIN, RG;ALDERSON, MR;PATRICIABECKMANN, M
通讯作者：
PATRICIABECKMANN, M
DOI：
10.1073/pnas.1521651112
发表时间：
2015-12-22
影响因子：
11.1
作者：
Casanova, Jean-Laurent
通讯作者：
Casanova, Jean-Laurent