EndoS Reduces the Pathogenicity of Anti-mCOL7 IgG through Reduced Binding of Immune Complexes

Endo-b-N-acetylglucosaminidase (EndoS) has been shown to act as a potent pathogen-derived immunomodulatory molecule in autoimmune diseases. Here we investigated how EndoS treatment reduces the pathogenicity of rabbit antimCOL7 IgG using different experimental models of epidermolysis bullosa acquisita (EBA). Our results show that the EndoS treatment does not interfere with the binding of the antibody to the antigen but reduces immune complex (IC)-mediated neutrophil activation by impairing the binding of the IC to FccR on neutrophils. On the basis of this newly identified EndoSmediated mechanism we hope to develop new strategies in the treatment of the disease. Citation: Yu X, Zheng J, Collin M, Schmidt E, Zillikens D, et al. (2014) EndoS Reduces the Pathogenicity of Anti-mCOL7 IgG through Reduced Binding of Immune Complexes to Neutrophils. PLoS ONE 9(2): e85317. doi:10.1371/journal.pone.0085317 Editor: Ger van Zandbergen, Federal Institute for Vaccines and Biomedicines, Germany Received August 29, 2013; Accepted November 25, 2013; Published February 4, 2014 Copyright: 2014 Yu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Deutsche Forschungsgemeinschaft, Cluster of Excellence ‘‘Inflammation at Interfaces’’ (EXC 306/1 and 2), Swedish Research Council (2010-57X-20240), the Foundations of Åke Wiberg, Alfred Österlund, King Gustaf V’s 80 years fund, Hansa Medical AB, and by the startup packages from the Medical College of Xiamen University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Hansa Medical AB (HM) (www.hansamedical.com) has filed patent applications for using EndoS as a treatment for antibody-mediated diseases (patents PCT/EP2007/010904 and PCT/EP2009/008215). MC is listed as one of the inventors on these applications and have a royalty agreement with HM. MC is a scientific consultant for HM through his sole proprietorship GlycImmun (GI) (www.glycimmun.com). HM and GI were not involved in any way in the design of the study, writing of the manuscript or the decision to publish. The authors will without exceptions adhere to all the PLOS ONE policies on sharing data and materials. * E-mail: [email protected]