Human complete Stat-1 deficiency is associated with defective type I and IIIFN responses in vitro but immunity to some low virulence viruses in vivo
Human complete Stat-1 deficiency is associated with defective type I and IIIFN responses in vitro but immunity to some low virulence viruses in vivo
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DOI：
10.4049/jimmunol.176.8.5078
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发表时间：
2006-04-15
影响因子：
4.4
通讯作者：
Arkwright, Peter D.
中科院分区：
文献类型：
--
作者：
Chapgier, Ariane;Wynn, Robert F.;Arkwright, Peter D.
常染色体隐性形式的人类完全Stat-1缺乏症是一种罕见的疾病，迄今为止在两名无关的患者中报道，这两名患者都发展为播散性卡介苗（BCG），随后在对病情进行详细研究之前死于病毒性疾病。它与通过含Stat-1的复合物对IFN-γ和IFN-α β的细胞应答受损有关。我们描述了第三个病人与完全的Stat-1缺乏症和播散性BCG感染，谁死了3个月后骨髓移植。患者的EBV转化的B细胞不表达Stat-1蛋白，也不激活含Stat-1的转录因子。我们还报告了Stat-1缺陷患者的新鲜血细胞对IFN-γ的体外反应和SV 40转化的成纤维细胞系对IFN-γ和IFN-α β的体外反应。在IL-12产生和HLA II类诱导方面，对IFN-γ没有反应，说明对BCG的脆弱性。此外，IFN-α β不抑制成纤维细胞中的HSV和水疱性口炎病毒复制，尽管在体内患者能够成功清除至少一些病毒。这项研究拓宽了我们对完全Stat-1缺乏症的理解，这是一种严重的先天性免疫缺陷。严重感染的儿童，尤其是但不限于分枝杆菌或病毒性疾病的患者，应怀疑存在Stat-1缺乏症。
The autosomal recessive form of human complete Stat-1 deficiency is a rare disorder, thus far reported in two unrelated patients, both of whom developed disseminated bacillus Calmette-Guerin (BCG) and subsequently died of viral illnesses before detailed studies of the condition could be performed. It is associated with impaired cellular responses to both IFN-gamma and IFN-alpha beta via Stat-1-containing complexes. We describe a third patient with complete Stat-1 deficiency and disseminated BCG infection, who died 3 mo after bone marrow transplantation. The patient's EBV-transformed B cells did not express Stat-1 protein and did not activate Stat-1-containing transcription factors. We also report the ex vivo responses of a Stat-1-deficient patient's fresh blood cells to IFN-gamma and the in vitro responses of a SV40-transformed fibroblastic cell line to IFN-gamma and IFN-alpha beta. There was no response to IFN-gamma in terms of IL-12 production and HLA class II induction, accounting for vulnerability to BCG. Moreover, IFN-alpha beta did not suppress HSV and vesicular stomatitis virus replication in fibroblasts, although in vivo the patient was able to successfully clear at least some viruses. This study broadens our understanding of complete Stat-1 deficiency, a severe form of innate immunodeficiency. Stat-1 deficiency should be suspected in children with severe infections, notably but not exclusively patients with mycobacterial or viral diseases.