The neonatal Fc receptor (FcRn) is an MHC class I–like molecule that is widely distributed in mammalian organs, tissues, and cells. FcRn is critical to maintaining immunoglobulin G (IgG) and albumin levels through rescuing these molecules from lysosomal degradation. IgG autoantibodies are associated with many autoimmune diseases, including myasthenia gravis (MG), a rare neuromuscular autoimmune disease that causes debilitating and, in its generalized form (gMG), potentially life-threatening muscle weakness. IgG autoantibodies are directly pathogenic in MG and target neuromuscular junction proteins, causing neuromuscular transmission failure. Treatment approaches that reduce autoantibody levels, such as therapeutic plasma exchange and intravenous immunoglobulin, have been shown to be effective for gMG patients but are not indicated as ongoing maintenance therapies and can be associated with burdensome side effects. Agents that block FcRn-mediated recycling of IgG represent a rational and promising approach for the treatment of gMG. Blocking FcRn allows targeted reduction of all IgG subtypes without decreasing concentrations of other Ig isotypes; therefore, FcRn blocking could be a safe and effective treatment strategy for a broad population of gMG patients. Several FcRn-blocking antibodies and one antibody Fc fragment have been developed and are currently in various stages of clinical development. This article describes the mechanism of FcRn blockade as a novel approach for IgG-mediated disease therapy and reviews promising clinical data using such FcRn blockers for the treatment of gMG.

新生儿 Fc 受体 (FcRn) 是一种 MHC I 类样分子，广泛分布于哺乳动物器官、组织和细胞中。FcRn 对于通过从溶酶体降解中拯救这些分子来维持免疫球蛋白 G (IgG) 和白蛋白水平至关重要。IgG 自身抗体与许多自身免疫性疾病有关，包括重症肌无力 (MG)，这是一种罕见的神经肌肉自身免疫性疾病，会导致衰弱，并且在其广义形式 (gMG) 中，可能会危及生命的肌肉无力。IgG 自身抗体在 MG 中直接致病，并靶向神经肌肉接头蛋白，导致神经肌肉传递失败。降低自身抗体水平的治疗方法，例如治疗性血浆置换和静脉注射免疫球蛋白，已被证明对 gMG 患者有效，但不指示作为持续的维持治疗，并且可能与繁重的副作用有关。阻断 FcRn 介导的 IgG 再循环的药物代表了治疗 gMG 的一种合理且有前景的方法。阻断 FcRn 可以有针对性地减少所有 IgG 亚型，而不会降低其他 Ig 同种型的浓度；因此，FcRn 阻断对于广泛的 gMG 患者可能是一种安全有效的治疗策略。已经开发了几种 FcRn 阻断抗体和一种抗体 Fc 片段，目前处于临床开发的不同阶段。本文描述了 FcRn 阻滞剂作为 IgG 介导的疾病治疗的新方法的机制，并回顾了使用此类 FcRn 阻滞剂治疗 gMG 的有希望的临床数据。