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

Mihai, Sidonia ; Albert, Heike ; Ludwig, Ralf J. ; Iwata, Hiroaki ; Björck, Lars LU ; Collin, Mattias LU and Nimmerjahn, Falk (2017) In Experimental Dermatology 26(8).
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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
EndoS, IdeS, Immunoglobulin G, Immunotherapy
in
Experimental Dermatology
volume
26
issue
8
publisher
Wiley-Blackwell
external identifiers
  • scopus:85007202913
  • pmid:27512946
  • wos:000406405200007
ISSN
0906-6705
DOI
10.1111/exd.13163
language
English
LU publication?
yes
id
8a341f7e-5042-4ae2-9efa-c521fa510714
date added to LUP
2017-01-20 13:43:37
date last changed
2021-03-03 02:20:37
@article{8a341f7e-5042-4ae2-9efa-c521fa510714,
  abstract     = {<p>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.</p>},
  author       = {Mihai, Sidonia and Albert, Heike and Ludwig, Ralf J. and Iwata, Hiroaki and Björck, Lars and Collin, Mattias and Nimmerjahn, Falk},
  issn         = {0906-6705},
  language     = {eng},
  number       = {8},
  publisher    = {Wiley-Blackwell},
  series       = {Experimental Dermatology},
  title        = {In vivo enzymatic modulation of IgG antibodies prevents immune complex-dependent skin injury},
  url          = {http://dx.doi.org/10.1111/exd.13163},
  doi          = {10.1111/exd.13163},
  volume       = {26},
  year         = {2017},
}