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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3481533
- author
- Hirose, Misa
; Vafia, Katerina
; Kalies, Kathrin
; Groth, Stephanie
; Westermann, Juergen
; Zillikens, Detlef
; Ludwig, Ralf J.
; Collin, Mattias
LU
and Schmidt, Enno
- organization
- publishing date
- 2012
- 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
- pmid:22652418
- 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
- 2016-04-01 10:21:29
- date last changed
- 2022-02-02 08:59:18
@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}},
keywords = {{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}},
doi = {{10.1016/j.jaut.2012.04.002}},
volume = {{39}},
year = {{2012}},
}