Pôle de Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain and Service de Rhumatologie, Clinique Universitaire Saint-Luc, Bruxelles, Belgium.Pôle de Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain and Service de Rhumatologie, Clinique Universitaire Saint-Luc, Bruxelles, Belgium.
Pôle de Rhumatologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain and Service de Rhumatologie, Clinique Universitaire Saint-Luc, Bruxelles, Belgium.
Rheumatology (Oxford). 2014 Aug;53(8):1369-76. doi: 10.1093/rheumatology/ket403. Epub 2013 Dec 15.
SLE is an autoimmune condition characterized by loss of tolerance to chromatin constituents and the production of ANAs. The majority of SLE patients display spontaneous expression of type I IFN-induced genes in circulating mononuclear cells and peripheral tissues, and type I IFNs play a role in the pathogenesis of the disease via the sustained activation of autoreactive T and B cells necessary for the production of pathogenic autoantibodies. Several IFN-blocking strategies are currently being evaluated in clinical trials: monoclonal antibodies directed against IFN-α and type I IFN-α receptor (IFNAR), as well as active immunization against IFN-α. This review describes the rationale behind these trials and the results obtained, and discusses the perspectives for further development of these drugs.
SLE 是一种自身免疫性疾病,其特征是对染色质成分的耐受性丧失和产生 ANA。大多数 SLE 患者在循环单核细胞和外周组织中表现出自发表达 I 型 IFN 诱导基因,I 型 IFN 通过持续激活自身反应性 T 和 B 细胞在疾病发病机制中发挥作用,这些细胞是产生致病性自身抗体所必需的。目前正在临床试验中评估几种 IFN 阻断策略:针对 IFN-α 和 I 型 IFN-α 受体 (IFNAR) 的单克隆抗体,以及针对 IFN-α 的主动免疫。本综述描述了这些试验背后的原理和获得的结果,并讨论了进一步开发这些药物的前景。