Inhibition of Maternal-to-Fetal Transfer of IgG Antibodies by FcRn Blockade in a Mouse Model of Arthrogryposis Multiplex Congenita

Neurol Neuroimmunol Neuroinflamm. 2021 May 27;8(4):e1011. doi: 10.1212/NXI.0000000000001011. Print 2021 Jul.

Abstract

Objective: To determine whether blocking the neonatal Fc receptor (FcRn) during gestation with an anti-FcRn monoclonal antibody (mAb) reduces transfer of pathogenic maternal antibodies in utero and decreases the likelihood of maternal antibody-mediated neonatal disease in the offspring.

Methods: Using a previously established maternal-to-fetal transfer mouse model of arthrogryposis multiplex congenita (AMC), we assessed the effect of 4470, an anti-FcRn mAb, on the transfer of total human immunoglobulin G (IgG) and specific acetylcholine receptor (AChR)-antibodies from mother to fetus, as well as its effect on the prevention of neurodevelopmental abnormalities in the offspring.

Results: Offspring of pregnant dams treated with 4470 during gestation showed a substantial reduction in total human IgG and AChR antibody levels compared with those treated with the isotype mAb control. Treatment with 4470 was also associated with a significant reduction in AMC-IgG-induced deformities (limb or spinal curve malformations) when compared with mAb control-exposed embryos and a nonsignificant increase in the percentage of fetuses showing spontaneous movements. 4470 exposure during pregnancy was not associated with changes in general parameters of maternal well-being or fetal development; indeed, male neonates showed faster weight gain and shorter time to reach developmental milestones.

Conclusions: FcRn blockade is a promising therapeutic strategy to prevent the occurrence of AMC and other human maternal autoantibody-related diseases in the offspring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Blocking / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage*
  • Arthrogryposis / prevention & control*
  • Autoantibodies / drug effects*
  • Disease Models, Animal
  • Female
  • Histocompatibility Antigens Class I / drug effects*
  • Humans
  • Immunoglobulin G
  • Maternal-Fetal Exchange*
  • Mice
  • Mice, Inbred ICR
  • Pregnancy
  • Receptors, Cholinergic / immunology
  • Receptors, Fc / drug effects*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Autoantibodies
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Receptors, Cholinergic
  • Receptors, Fc
  • Fc receptor, neonatal