• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of neuroinflammation >An autoinflammatory neurological disease due to interleukin 6 hypersecretion
【24h】

An autoinflammatory neurological disease due to interleukin 6 hypersecretion

机译：白细胞介素6分泌过多引起的自身炎症性神经疾病

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they are also characterized by non-neurological manifestations. In this work we studied a 30-year-old man who had a chronic disease characterized by meningitis, progressive hearing loss, persistently raised inflammatory markers and diffuse leukoencephalopathy on brain MRI. He also suffered from chronic recurrent osteomyelitis of the mandible. The hypothesis of an autoinflammatory disease prompted us to test for the presence of mutations in interleukin-1?pathway genes and to investigate the function of this pathway in the mononuclear cells obtained from the patient. Search for mutations in genes associated with interleukin-1?pathway demonstrated a novel NLRP3 (CIAS1) mutation (p.I288M) and a previously described MEFV mutation (p.R761H), but their combination was found to be non-pathogenic. On the other hand, we uncovered a selective interleukin-6 hypersecretion within the central nervous system as the likely pathogenic mechanism. This is also supported by the response to the anti-interleukin-6?receptor monoclonal antibody tocilizumab, but not to the recombinant interleukin-1?receptor antagonist anakinra. Exome sequencing failed to identify mutations in other genes known to be involved in autoinflammatory diseases. We propose that the disease described in this patient might be a prototype of a novel category of autoinflammatory diseases characterized by prominent neurological involvement.
机译：自身炎症性疾病是罕见疾病，其特征在于明显的无缘无故的炎症，而没有高滴度自身抗体或抗原特异性T细胞。它们可能引起神经系统表现，例如脑膜炎和听力下降，但它们的特征还在于非神经系统表现。在这项工作中，我们研究了一名30岁的男子，该男子患有脑膜MRI表现为脑膜炎，进行性听力减退，炎症标志物持续升高和弥漫性白质脑病的慢性疾病。他还患有下颌骨慢性复发性骨髓炎。自身炎症性疾病的假说促使我们测试白介素-1β通路基因中突变的存在，并研究该通路在从患者获得的单核细胞中的功能。在与白介素-1α通路相关的基因中进行突变的搜索显示了一种新的NLRP3（CIAS1）突变（p.I288M）和先前描述的MEFV突变（p.R761H），但是发现它们的组合是非致病性的。另一方面，我们发现中枢神经系统内选择性白介素6过度分泌是可能的致病机制。对抗白介素-6α受体单克隆抗体托珠单抗的应答也支持了这一点，但对重组白介素-1α受体拮抗剂anakinra却没有应答。外显子组测序未能鉴定出已知与自身炎症性疾病有关的其他基因的突变。我们建议在该患者中描述的疾病可能是特征为神经系统受累的新型自发性疾病的原型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号