title: IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid.
abstract: The IgG4 subclass of antibodies exhibits unique characteristics that suggest it may function in an immunoregulatory capacity. The inhibitory function of IgG4 has been well documented in allergic disease by the demonstration of IgG4 blocking antibodies, but similar functions have not been explored in autoimmune disease. Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease characterized by autoantibodies directed against BP180 and an inflammatory infiltrate including eosinophils and neutrophils. Animal models have revealed that the NC16A region within BP180 harbors the critical epitopes necessary for autoantibody mediated disease induction. BP180 NC16A-specific IgG belong to the IgG1, IgG3, and IgG4 subclasses. The purpose of this study was to determine effector functions of different IgG subclasses of NC16A-specific autoantibodies in BP. We find that IgG4 anti-NC16A autoantibodies inhibit the binding of IgG1 and IgG3 autoantibodies to the NC16A region. Moreover, IgG4 anti-NC16A blocks IgG1 and IgG3 induced complement fixation, neutrophil infiltration, and blister formation clinically and histologically in a dose-dependent manner following passive transfer to humanized BP180-NC16A mice. These findings highlight the inhibitory role of IgG4 in autoimmune disease and have important implications for the treatment of BP as well as other antibody mediated inflammatory and autoimmune diseases.
authors.affiliation: Department of Dermatology and Venereology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Departments of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Yagang
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Departments of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Flor
authors.initials: F
authors.lastname: Evangelista
authors.affiliation: Departments of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Culton
authors.affiliation: Department of Dermatology, Hospital General de Granollers, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Guilabert
authors.affiliation: Departments of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Departments of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Departments of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Diaz
authors.affiliation: Departments of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Departments of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: zhi_liu@med.unc.edu.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D003168:Complement Fixation Tests; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D051379:Mice; D024041:Non-Fibrillar Collagens / Q000276:immunology*; D010391:Pemphigoid, Bullous / Q000097:blood / Q000276:immunology*; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D007074:Immunoglobulin G; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII
keywords: Autoimmune; Bullous pemphigoid; IgG4; Inhibitory