Mathian Alexis, Felten Renaud, Alarcon-Riquelme Marta E, Psarras Antony, Mertz Philippe, Chasset François, Vital Edward M, Arnaud Laurent
Assistance publique-Hôpitaux de Paris (AP-HP), groupement hospitalier Pitié-Salpêtrière, centre de référence pour le Lupus, le syndrome des anti-phospholipides et autres maladies auto-immunes rares, service de médecine interne 2, institut E3M, Inserm, centre d'immunologie et des maladies infectieuses (CIMI-Paris), 47-83, boulevard de l'hôpital, 75651 Paris cedex 13, France.
Centre d'investigation clinique, Inserm 1434, nouvel hôpital civil, quai Louis-Pasteur, 67000 Strasbourg, France; Département universitaire de pharmacologie-addictologie, toxicologie et thérapeutique, université de Strasbourg, 4, rue Kirschleger, 67000 Strasbourg, France; Service de rhumatologie, centre national de référence maladies rares Est Sud-Ouest (RESO), hôpitaux universitaires de Strasbourg, université de Strasbourg, 1, avenue Molière, 67200 Strasbourg, France.
Joint Bone Spine. 2024 Mar;91(2):105627. doi: 10.1016/j.jbspin.2023.105627. Epub 2023 Aug 26.
The improved understanding of the molecular basis of innate immunity have led to the identification of type I interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of several Immune-mediated inflammatory diseases (IMIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis and Sjögren's syndrome. Here, we review the main data regarding the opportunity to target type I IFNs for the treatment of IMIDs. Type I IFNs and their downstream pathways can be targeted pharmacologically in several manners. One approach is to use monoclonal antibodies against IFNs or the IFN-receptors (IFNARs, such as with anifrolumab). The downstream signaling pathways of type I IFNs also contain several targets of interest in IMIDs, such as JAK1 and Tyk2. Of these, anifrolumab is licensed and JAK1/Tyk2 inhibitors are in phase III trials in SLE. Targeting IFN-Is for the treatment of SLE is already a reality and in the near future may prove useful in other IMIDs. IFN assays will find a role in routine clinical practice for the care of IMIDs as further validation work is completed and a greater range of targeted therapies becomes available.
对固有免疫分子基础的深入理解,已促使人们将I型干扰素(IFN),尤其是IFN-α,确定为系统性红斑狼疮(SLE)、系统性硬化症、炎性肌病和干燥综合征等多种免疫介导的炎性疾病(IMID)发病机制中的核心介质。在此,我们综述了有关靶向I型IFN治疗IMID的可能性的主要数据。I型IFN及其下游通路可以通过多种方式进行药物靶向。一种方法是使用针对IFN或IFN受体(IFNAR,如阿尼鲁单抗)的单克隆抗体。I型IFN的下游信号通路在IMID中也包含几个有意义的靶点,如JAK1和Tyk2。其中,阿尼鲁单抗已获许可,JAK1/Tyk2抑制剂正处于SLE的III期试验中。靶向I型IFN治疗SLE已成为现实,在不久的将来可能对其他IMID也有用。随着进一步验证工作的完成以及更多靶向治疗药物的出现,IFN检测将在IMID的常规临床护理中发挥作用。