Enzymatic autoantibody glycan hydrolysis alleviates autoimmunity against type VII collagen

Research output: Contribution to journalArticle

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.

Details

Authors
  • Misa Hirose
  • Katerina Vafia
  • Kathrin Kalies
  • Stephanie Groth
  • Juergen Westermann
  • Detlef Zillikens
  • Ralf J. Ludwig
  • Mattias Collin
  • Enno Schmidt
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity

Keywords

  • Autoantibody, Bullous, EndoS, IgG, Hydrolysis
Original languageEnglish
Pages (from-to)304-314
JournalJournal of Autoimmunity
Volume39
Issue number4
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes