IgG regulation through FcRn blocking: A novel mechanism for the treatment of myasthenia gravis

J Neurol Sci. 2021 Nov 15;430:118074. doi: 10.1016/j.jns.2021.118074. Epub 2021 Sep 13.


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.

Keywords: Autoimmune disease; Clinical neurology; Clinical trials; Myasthenia; Neuromuscular disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantibodies
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Immunoglobulin G*
  • Immunoglobulins, Intravenous / therapeutic use
  • Myasthenia Gravis* / drug therapy


  • Autoantibodies
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Immunoglobulins, Intravenous