In vivo enzymatic modulation of IgG antibodies prevents immune complex-dependent skin injury

Sidonia Mihai*, Heike Albert, Ralf J. Ludwig, Hiroaki Iwata, Lars Björck, Mattias Collin, Falk Nimmerjahn

*Corresponding author for this work
1 Citation (Scopus)

Abstract

IgG antibodies are potent inducers of proinflammatory responses by cross-linking Fc receptors on innate immune effector cells resulting in tissue injury. The recently discovered enzymes endoglycosidase S (EndoS) and IgG-degrading enzyme (IdeS) of Streptococcus pyogenes are able to modulate the interaction between IgG antibodies and the Fc receptors, by hydrolysis of the glycan associated with the heavy chain of the IgG molecule (EndoS), or cleavage in the hinge region of the heavy IgG chain (IdeS). In this work, we investigated their ability to inhibit damage mediated by skin-bound antibodies in vivo in two different experimental models, the Arthus reaction, and epidermolysis bullosa acquisita, an autoimmune blistering skin disease associated with autoantibodies against type VII collagen. We demonstrate that both enzymes efficiently interfere with IgG-mediated proinflammatory processes, offering a great asset to specifically target pathological IgG antibodies in the skin and holding great promise for future applications in human therapy.

Original languageEnglish
JournalExperimental Dermatology
Volume26
Issue number8
Pages (from-to)691-696
Number of pages6
ISSN0906-6705
DOIs
Publication statusPublished - 01.08.2017

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