title: In vivo enzymatic modulation of IgG antibodies prevents immune complex-dependent skin injury.
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.
authors: Department of Biology, Institute of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.|Department of Clinical Chemistry, University Hospital Erlangen, Erlangen, Germany.
authors: Sidonia
authors: S
authors: Mihai
authors: Department of Biology, Institute of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Heike
authors: H
authors: Albert
authors: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors: Ralf J
authors: RJ
authors: Ludwig
authors: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors: Hiroaki
authors: H
authors: Iwata
authors: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors: Lars
authors: L
authors: Björck
authors: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors: Mattias
authors: M
authors: Collin
authors: Department of Biology, Institute of Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: Falk
authors: F
authors: Nimmerjahn
mesh_terms: D000818:Animals; D001183:Arthus Reaction / Q000517:prevention & control*; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D024143:Collagen Type VII / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D016107:Epidermolysis Bullosa Acquisita / Q000517:prevention & control*; D005260:Female; D006026:Glycoside Hydrolases / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000378:metabolism; D008810:Mice, Inbred C57BL
chemical_list: D001426:Bacterial Proteins; D024143:Collagen Type VII; D007074:Immunoglobulin G; C442815:Mac-1-like protein, Streptococcus; D006026:Glycoside Hydrolases; C431325:NDOS protein, Streptococcus pyogenes
keywords: EndoS; IdeS; immunoglobulin G; immunotherapy