Vial G, Gensous N, Duffau P
Department of Internal Medicine and Clinical Immunology, University Hospital Centre of Bordeaux, Saint-André Hospital, 33000 Bordeaux, France.
Department of Internal Medicine and Clinical Immunology, University Hospital Centre of Bordeaux, Saint-André Hospital, 33000 Bordeaux, France.
Rev Med Interne. 2021 Oct;42(10):722-728. doi: 10.1016/j.revmed.2021.02.005. Epub 2021 Mar 2.
The CD40-CD40 ligand (CD40L) pathway is a backbone of communication between cells of the immune system. It makes it possible to generate a proinflammatory signal and thus participates in the pathogenesis of dysimmune diseases, transplant rejection and atherosclerosis. Because of this therapeutic target of choice, several generations of anti-CD40L monoclonal antibodies have emerged since the 1990s. The first generation of antibodies was responsible for thromboembolic toxicity for which the mechanisms are starting to be defined. New generations of antibodies were designed to overcome this toxicity and are still being developed in lupus, rheumatoid arthritis, Sjogren's syndrome or immunologic thrombocytopenia. In addition to these targeted therapies, there are data suggesting the impact of several drugs among molecules used in cardiology and clinical immunology on the level of CD40L. The objective of this review is to recall the clinical issues related to the CD40-CD40L axis and to present current or future treatments that block CD40L which would allow clinicians to diversify their options for managing dysimmune diseases.
CD40-CD40配体(CD40L)通路是免疫系统细胞间通讯的支柱。它使得促炎信号得以产生,从而参与免疫失调疾病、移植排斥和动脉粥样硬化的发病机制。由于这一备受青睐的治疗靶点,自20世纪90年代以来已出现了几代抗CD40L单克隆抗体。第一代抗体导致了血栓栓塞毒性,其机制正开始得到明确。新一代抗体旨在克服这种毒性,目前仍在狼疮、类风湿关节炎、干燥综合征或免疫性血小板减少症中进行研发。除了这些靶向治疗外,有数据表明,心脏病学和临床免疫学中使用的几种药物对CD40L水平有影响。本综述的目的是回顾与CD40-CD40L轴相关的临床问题,并介绍目前或未来阻断CD40L的治疗方法,这将使临床医生在管理免疫失调疾病时有更多样化的选择。