Autoantibody depletion ameliorates disease in murine experimental autoimmune encephalomyelitis

MAbs. Sep-Oct 2013;5(5):655-9. doi: 10.4161/mabs.25439. Epub 2013 Jun 19.

Abstract

Much data support a role for central nervous system antigen-specific antibodies in the pathogenesis of multiple sclerosis (MS). The effects of inducing a decrease in (auto)antibody levels on MS or experimental autoimmune encephalomyelitis (EAE) through specific blockade of FcRn, however, remain unexplored. We recently developed engineered antibodies that lower endogenous IgG levels by competing for binding to FcRn. These Abdegs ("antibodies that enhance IgG degradation") can be used to directly assess the effect of decreased antibody levels in inflammatory diseases. In the current study, we show that Abdeg delivery ameliorates disease in an EAE model that is antibody dependent. Abdegs could therefore have promise as therapeutic agents for MS.

Keywords: EAE; FcRn; autoantibody; engineered antibodies; therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / genetics
  • Antibodies / immunology*
  • Antibodies / metabolism
  • Autoantibodies / immunology*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Female
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / prevention & control
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Protein Binding / drug effects
  • Protein Binding / immunology
  • Protein Engineering / methods*
  • Receptors, Fc / immunology
  • Receptors, Fc / metabolism
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Antibodies
  • Autoantibodies
  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Fc
  • Recombinant Proteins
  • Fc receptor, neonatal