Autoantibody depletion ameliorates disease in murine experimental autoimmune encephalomyelitis

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: :

• autoantibody
• EAE
• FcRn
• engineered antibodies
• therapy

Disclosure of Potential Conflicts of Interest

E.S.W. is an inventor on a patent (owned by UT Southwestern Medical Center) related to the use of Abdegs as FcRn inhibitors. None of the other authors on this manuscript have any financial conflict of interest.

Acknowledgments

We are grateful to Ramraj Velmurugan for assistance with fluorescence microscopy and to Dr Stephen Anthony for developing a computational algorithm for mouse grouping. This work was supported in part by grants from the National Multiple Sclerosis Society (RG 4308).

Notes

† These authors contributed equally to this work.