IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid

被引：37

作者：

Zuo, Yagang ^{[1
,2
,3
]}

Evangelista, Flor ^{[3
,7
]}

Culton, Donna ^{[3
]}

Guilabert, Antonio ^{[6
]}

Lin, Lin ^{[3
]}

Li, Ning ^{[3
]}

Diaz, Luis ^{[3
]}

Liu, Zhi ^{[3
,4
,5
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Dermatol & Venereol, Beijing 100730, Peoples R China

[2] Peking Union Med Coll, Beijing 100730, Peoples R China

[3] Univ N Carolina, Dept Dermatol, 2360 Genome Sci Bldg,CB 7287, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Dept Immunol, Chapel Hill, NC 27599 USA

[6] Hosp Gen Granollers, Dept Dermatol, Barcelona, Spain

[7] Univ Privada Antenor Orrego, Lab Invest Multidisciplinaria, Trujillo, Peru

来源：

JOURNAL OF AUTOIMMUNITY | 2016年 / 73卷

关键词：

IgG4; Bullous pemphigoid; Inhibitory; Autoimmune; THROMBOTIC THROMBOCYTOPENIC PURPURA; FC-GAMMA RECEPTORS; FAB-ARM EXCHANGE; IGG4-RELATED DISEASE; SUBCLASS DISTRIBUTION; COMPLEMENT-SYSTEM; IMMUNOGLOBULIN G4; BP180; ECTODOMAIN; ANTIBODIES; IMMUNOTHERAPY;

D O I：

10.1016/j.jaut.2016.06.019

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 BR. 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. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：111 / 119

页数：9

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