Potent induction of IFN-alpha and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus.
Potent induction of IFN-alpha and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus.
复制标题
DOI：
10.4049/jimmunol.182.2.1192
复制
发表时间：
2009-01-15
期刊：
影响因子：
--
通讯作者：
Elkon KB
中科院分区：
文献类型：
--
作者：
Santer DM;Yoshio T;Minota S;Möller T;Elkon KB
系统性红斑狼疮（NPSLE）3中的神经精神疾病是一种了解不多，但可能致命的疾病表现。自身抗体的致病作用被怀疑，但机制尚不清楚。由于SLE中的免疫复合物可以刺激IFN-α，并且在人类和小鼠中有强有力的证据表明IFN-α可以引起神经精神症状，因此我们询问NPSLE患者血清和/或脑脊液（CSF）是否含有异常高的IFN-α诱导活性。在含有浆细胞样树突状细胞和抗原来源的生物测定中，与多发性硬化症患者或其他自身免疫性疾病对照的CSF相比，NPSLE CSF诱导的IFN-α显著更高。当对IgG浓度进行标准化时，由于血清中存在抑制剂，NPSLE CSF诱导IFN-α的效力是配对血清的800倍。在生物测定中，对Ig缺乏患者血清、正常血清中IgG的消耗以及向NPSLE CSF和血清中添加纯化IgG的分析显示，IgG组分本身中含有一种抑制剂。除IFN-α外，CSF自身抗体形成的免疫复合物产生的IFN-γ诱导蛋白10（IP-10/CXCL）、IL-8和MCP-1水平显著升高，据报道，所有这些在NPSLE患者的CSF中均升高。总之，这些发现与NPSLE的两步模型一致，其中CSF自身抗体与神经细胞毒性Ab或其他脑细胞损伤释放的Ag结合，所得免疫复合物刺激IFN-α和促炎细胞因子和趋化因子。
Neuropsychiatric disease in systemic lupus erythematosus (NPSLE)3 is a poorly understood, but potentially fatal, disease manifestation. A pathogenetic role for autoantibodies is suspected, but the mechanism is unclear. Since immune complexes in SLE can stimulate IFN-α and there is strong evidence in humans and in mice that IFN-α can cause neuropsychiatric manifestations, we asked whether NPSLE patient serum and/or cerebrospinal fluid (CSF) contain abnormally high IFN-α-inducing activity. In a bioassay containing plasmacytoid dendritic cells and a source of Ag, NPSLE CSF induced significantly higher IFN-α compared with CSF from patients with multiple sclerosis or other autoimmune disease controls. When normalized for IgG concentration, NPSLE CSF was 800-fold more potent at inducing IFN-α compared with paired serum due to inhibitors present in serum. Analysis of Ig-deficient patient serum, depletion of IgG from normal serum, as well as addition of purified IgG to NPSLE CSF and serum in the bioassays revealed that one inhibitor was contained within the IgG fraction itself. In addition to IFN-α, immune complexes formed by CSF autoantibodies produced significantly increased levels of IFN-γ-inducible protein 10 (IP-10/CXCL), IL-8, and MCP-1, all of which have been reported to be elevated in CSF from NPSLE patients. Taken together, these findings are consistent with a two-step model of NPSLE whereby CSF autoantibodies bind to Ags released by neurocytotoxic Abs or other brain cell injury, and the resulting immune complexes stimulate IFN-α and proinflammatory cytokines and chemokines.
登录
查看更多内容
影响因子：
2.6
作者：
Levy, Y;Sherer, Y;Shoenfeld, Y
通讯作者：
Shoenfeld, Y
影响因子：
4.8
作者：
Linker, Ralf A.;Gold, Ralf
通讯作者：
Gold, Ralf
DOI：
10.1056/nejmoa0706383
发表时间：
2008-02-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hauser, Stephen L;Waubant, Emmanuelle;Smith, Craig H
通讯作者：
Smith, Craig H
影响因子：
30.8
作者：
Crow, Yanick J.;Leitch, Andrea;Jackson, Andrew P.
通讯作者：
Jackson, Andrew P.
影响因子：
32.4
作者：
Christensen, Sean R.;Shupe, Jonathan;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.