Targeting the neonatal Fc receptor (FcRn) to treat autoimmune diseases and maternal-fetal immune cytopenias

Transfusion. 2021 May;61(5):1350-1354. doi: 10.1111/trf.16341. Epub 2021 Mar 2.

Abstract

FcRn, a non-classical Fc gamma (γ) receptor (FcγR) with near ubiquitous expression, plays key roles in disease pathogenesis and progression though immunoglobulin G (IgG) transport, IgG recycling, and IgG-immune complex clearance. FcRn function can be inhibited using IgG-based and non-IgG-based antagonists, by exploiting the pH-dependent binding affinity of FcRn for the IgG Fc region. FcRn therapeutics have shown promise in murine models and human clinical trials for autoimmune diseases and maternal-fetal immune cytopenias; they appear safe, well-tolerated, and reduce circulating IgG levels. Compared to traditional therapeutics, inhibiting FcRn has fewer adverse side effects and represents a new approach that is less invasive, time-consuming, and costly.

Keywords: AIHA/drug-induced IHA; HDN; immune thrombocytopenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Autoimmunity / drug effects
  • Drug Development
  • Female
  • Fetus / immunology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Molecular Targeted Therapy
  • Pregnancy
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy*
  • Purpura, Thrombocytopenic, Idiopathic / immunology
  • Receptors, Fc / antagonists & inhibitors*
  • Receptors, Fc / immunology

Substances

  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Receptors, Fc
  • Fc receptor, neonatal