Journal
JOURNAL OF AUTOIMMUNITY
Volume 39, Issue 4, Pages 304-314Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2012.04.002
Keywords
Autoantibody; Bullous; EndoS; IgG; Hydrolysis
Categories
Funding
- Hansa Medical AB
- Excellence Cluster Inflammation at Interfaces [EXC306/1]
- Novartis Pharma
- Swedish Research Council [2005-4791, 2010-57X-20240]
- Foundation of Crafoord
- Foundation of Hedberg
- Foundation of Bergvall
- Foundation of Osterlund
- Foundation of Wiberg
- Foundation of Soderberg
- Swedish Society for Medicine
- Royal Physiografic Society, King Gustaf V's Memorial Fund
- Swedish Rheumatism Association
- Medical Faculty at Lund University
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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.
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