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Enzymatic autoantibody glycan hydrolysis alleviates autoimmunity against type VII collagen

Hirose, Misa; Vafia, Katerina; Kalies, Kathrin; Groth, Stephanie; Westermann, Juergen; Zillikens, Detlef; Ludwig, Ralf J.; Collin, Mattias LU and Schmidt, Enno (2012) In Journal of Autoimmunity 39(4). p.304-314
Abstract
Autoantibody-mediated diseases comprise a heterogeneous group of disorders in which the pathogenic potential of autoantibodies has been clearly demonstrated. In general, their treatment relies on the long-term use of systemic corticosteroids and other immunosuppressants that are associated with considerable adverse reactions. EndoS, an endoglycosidase derived from Streptococcus pyogenes, specifically hydrolyzes the N-linked glycan of native IgG and has previously been shown to modulate the interaction between the Fc portion of autoantibody and Fc gamma receptors on leukocytes. Here, different models of autoimmunity to type VII collagen, a structural protein of the dermal-epidermal junction (DEJ), were employed to explore the therapeutic... (More)
Autoantibody-mediated diseases comprise a heterogeneous group of disorders in which the pathogenic potential of autoantibodies has been clearly demonstrated. In general, their treatment relies on the long-term use of systemic corticosteroids and other immunosuppressants that are associated with considerable adverse reactions. EndoS, an endoglycosidase derived from Streptococcus pyogenes, specifically hydrolyzes the N-linked glycan of native IgG and has previously been shown to modulate the interaction between the Fc portion of autoantibody and Fc gamma receptors on leukocytes. Here, different models of autoimmunity to type VII collagen, a structural protein of the dermal-epidermal junction (DEJ), were employed to explore the therapeutic potential of EndoS. First, pretreatment of otherwise pathogenic anti-murine type VII collagen (mCOL7) IgG with EndoS significantly reduced split formation at the DEJ in cryosections of murine skin and abrogated clinical disease in mice. Next, the effect of EndoS was also seen when the enzyme was injected into mice after pathogenic anti-mCOL7 IgG had been administered. Finally, to mimic the patient situation even closer, EndoS was applied in mice that had already developed clinical disease after immunization with mCOL7. In all EndoS-treated mice, disease progression was stopped, and in the majority of mice, clinical disease even regressed. Of note, EndoS was shown to hydrolyze already in vivo-bound pathogenic autoantibodies. In addition, EndoS treatment decreased lesional expression of activating Fc gamma Rs while increasing Fc gamma RIIB expression. (C) 2012 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoantibody, Bullous, EndoS, IgG, Hydrolysis
in
Journal of Autoimmunity
volume
39
issue
4
pages
304 - 314
publisher
Elsevier
external identifiers
  • wos:000313465800007
  • scopus:84869878298
ISSN
0896-8411
DOI
10.1016/j.jaut.2012.04.002
language
English
LU publication?
yes
id
8fcb67cf-9170-4103-9522-a6a8ab0f71e5 (old id 3481533)
date added to LUP
2013-03-01 07:50:06
date last changed
2017-08-06 03:11:23
@article{8fcb67cf-9170-4103-9522-a6a8ab0f71e5,
  abstract     = {Autoantibody-mediated diseases comprise a heterogeneous group of disorders in which the pathogenic potential of autoantibodies has been clearly demonstrated. In general, their treatment relies on the long-term use of systemic corticosteroids and other immunosuppressants that are associated with considerable adverse reactions. EndoS, an endoglycosidase derived from Streptococcus pyogenes, specifically hydrolyzes the N-linked glycan of native IgG and has previously been shown to modulate the interaction between the Fc portion of autoantibody and Fc gamma receptors on leukocytes. Here, different models of autoimmunity to type VII collagen, a structural protein of the dermal-epidermal junction (DEJ), were employed to explore the therapeutic potential of EndoS. First, pretreatment of otherwise pathogenic anti-murine type VII collagen (mCOL7) IgG with EndoS significantly reduced split formation at the DEJ in cryosections of murine skin and abrogated clinical disease in mice. Next, the effect of EndoS was also seen when the enzyme was injected into mice after pathogenic anti-mCOL7 IgG had been administered. Finally, to mimic the patient situation even closer, EndoS was applied in mice that had already developed clinical disease after immunization with mCOL7. In all EndoS-treated mice, disease progression was stopped, and in the majority of mice, clinical disease even regressed. Of note, EndoS was shown to hydrolyze already in vivo-bound pathogenic autoantibodies. In addition, EndoS treatment decreased lesional expression of activating Fc gamma Rs while increasing Fc gamma RIIB expression. (C) 2012 Elsevier Ltd. All rights reserved.},
  author       = {Hirose, Misa and Vafia, Katerina and Kalies, Kathrin and Groth, Stephanie and Westermann, Juergen and Zillikens, Detlef and Ludwig, Ralf J. and Collin, Mattias and Schmidt, Enno},
  issn         = {0896-8411},
  keyword      = {Autoantibody,Bullous,EndoS,IgG,Hydrolysis},
  language     = {eng},
  number       = {4},
  pages        = {304--314},
  publisher    = {Elsevier},
  series       = {Journal of Autoimmunity},
  title        = {Enzymatic autoantibody glycan hydrolysis alleviates autoimmunity against type VII collagen},
  url          = {http://dx.doi.org/10.1016/j.jaut.2012.04.002},
  volume       = {39},
  year         = {2012},
}