EndoS reduces the pathogenicity of anti-mCOL7 IgG through reduced binding of immune complexes to neutrophils

Xinhua Yu; Junfeng Zheng; Mattias Collin; Enno Schmidt; Detlef Zillikens; Frank Petersen

doi:10.1371/journal.pone.0085317

EndoS reduces the pathogenicity of anti-mCOL7 IgG through reduced binding of immune complexes to neutrophils

PLoS One. 2014 Feb 4;9(2):e85317. doi: 10.1371/journal.pone.0085317. eCollection 2014.

Authors

Xinhua Yu¹, Junfeng Zheng², Mattias Collin³, Enno Schmidt⁴, Detlef Zillikens⁴, Frank Petersen⁵

Affiliations

¹ Priority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany ; Laboratory of Autoimmunity, The Medical College of Xiamen University, Xiamen University, Xiamen, China.
² Laboratory of Autoimmunity, The Medical College of Xiamen University, Xiamen University, Xiamen, China.
³ Division of Infection Medicine, Department of Clinical Science, Lund University, Lund, Sweden.
⁴ Department of Dermatology, University of Lübeck, Lübeck, Germany.
⁵ Priority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany.

Abstract

Endo-β-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 anti-mCOL7 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 FcγR on neutrophils. On the basis of this newly identified EndoS-mediated mechanism we hope to develop new strategies in the treatment of the disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigen-Antibody Complex / immunology*
Antigens / metabolism
Collagen Type VII / immunology*
Disease Models, Animal
Epidermolysis Bullosa Acquisita / pathology
Humans
Immunoglobulin G / immunology*
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / metabolism*
Mice, Inbred C57BL
Neutrophil Activation
Neutrophils / immunology*
Protein Binding
Rabbits

Substances

Antigen-Antibody Complex
Antigens
Collagen Type VII
Immunoglobulin G
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase

Grants and 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.