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Home / Spectrum / Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti-aquaporin-4 igginto therapeutic antibody – Tradtrantip – Annals of Neurology – Wiley Online Library

Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti-aquaporin-4 igginto therapeutic antibody – Tradtrantip – Annals of Neurology – Wiley Online Library

Abstract

Objective.

Neuromyelitisoptica (NMO) is caused by binding of pathogenic autoantibodies (NMO-IgG) to aquaporin-4 (AQP4) on astrocytes, which initiates complement-dependent cytotoxicity (CDC) and inflammation. We recently introduced mutated antibody (aquaporumab) and small-molecule blocker strategies for therapy of NMO, based on prevention of NMO-IgG binding to AQP4. Here, we investigated an alternative strategy involving neutralization of NMO-IgGeffector function by selective IgGheavy-chain deglycosylation with bacteria-derived endoglycosidase S (EndoS).

Methods.

Cytotoxicity and NMO pathology were measured in cell and spinal cord slice cultures, and in mice exposed to control orEndoS-treated NMO-IgG.

Results.

EndoS treatment of NMO patient serum reduced by >95 % CDC and antibody-dependent cell-mediated cytotoxicity (ADCC), without impairment of NMO-IgGbinding to AQP4.Cytotoxicity was also prevented by addition of EndoS after NMO-IgG binding to AQP4. The EndoS-treated, non-pathogenic NMO-IgG competitively displaced pathogenic NMO-IgG bound to AQP4, and prevented NMO pathology in spinal cord slice culture and mouse models of NMO.

Interpretation.

EndoSdeglycosylation converts pathogenic NMO-IgGautoantibodiesinto therapeutic blocking antibodies.EndoS treatment of bloodmay be beneficial in NMO, which may be accomplished, for example, by therapeutic apheresis using surface-immobilized EndoS. Ann Neurol 2012.

Read More: Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti-aquaporin-4 igginto therapeutic antibody – Tradtrantip – Annals of Neurology – Wiley Online Library

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