Misra Durga Prasanna, Negi Vir Singh
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India.
Mediterr J Rheumatol. 2017 Mar 28;28(1):13-19. doi: 10.31138/mjr.28.1.13. eCollection 2017 Mar.
Type I interferons secreted by plasmacytoid dendritic cells (pDCs) play a crucial role in the pathogenesis of systemic lupus erythematosus by driving the formation of autoantibodies against nuclear debris. Inherited mutations causing activation of the Type I interferon pathway result in a phenotype of systemic autoimmunity which resembles some of the manifestations of lupus. Patients with lupus have increased expression of interferon-stimulated genes in the peripheral blood mononuclear cells which is abrogated following immunosuppressive treatment. Recent therapeutic approaches have involved monoclonal antibodies directly targeting interferon alpha (sifalimumab, rontalizumab) or the use of interferon alpha kinoid to stimulate endogenous production of anti-interferon antibodies in lupus. Other drugs used in lupus such as hydroxychloroquine and bortezomib also reduce circulating levels of type I interferons. Newer therapeutic strategies being investigated in preclinical models of lupus that reduce the production of Type I interferons include dihydroartemisinin, Bruton's tyrosine kinase antagonists, Bcl-2 antagonists and sphingosine-1 phosphate agonists.
浆细胞样树突状细胞（pDCs）分泌的I型干扰素通过驱动针对核碎片的自身抗体形成，在系统性红斑狼疮的发病机制中起关键作用。导致I型干扰素途径激活的遗传突变会导致一种系统性自身免疫表型，类似于狼疮的一些表现。狼疮患者外周血单个核细胞中干扰素刺激基因的表达增加，免疫抑制治疗后这种表达会被消除。最近的治疗方法包括直接靶向干扰素α的单克隆抗体（西法莫单抗、罗坦利单抗），或使用干扰素α类毒素来刺激狼疮患者体内抗干扰素抗体的内源性产生。狼疮治疗中使用的其他药物，如羟氯喹和硼替佐米，也能降低I型干扰素的循环水平。在狼疮临床前模型中研究的、减少I型干扰素产生的新型治疗策略包括双氢青蒿素、布鲁顿酪氨酸激酶拮抗剂、Bcl-2拮抗剂和鞘氨醇-1-磷酸激动剂。
