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Enzymatic autoantibody glycan hydrolysis alleviates autoimmunity against type VII collagen.
MedLine Citation:
PMID:  22652418     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 Fcγ 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 FcγRs while increasing FcγRIIB expression.
Authors:
Misa Hirose; Katerina Vafia; Kathrin Kalies; Stephanie Groth; Jürgen Westermann; Detlef Zillikens; Ralf J Ludwig; Mattias Collin; Enno Schmidt
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-30
Journal Detail:
Title:  Journal of autoimmunity     Volume:  -     ISSN:  1095-9157     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-6-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8812164     Medline TA:  J Autoimmun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, Lübeck D-23538, Germany.
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