Neonatal Fc receptor deficiency protects from tissue injury in experimental epidermolysis bullosa acquisita.
Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease caused by autoantibodies against type VII collagen. The neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and thus controls serum levels of antibodies. In this study, we investigated the effects of FcRn deficiency on the levels of autoantibodies against type VII collagen and blistering in EBA. For this purpose, rabbit IgG against murine type VII collagen was injected into FcRn-deficient and wild-type (n = 10 per group) mice. Enzyme-linked immunosorbent assay levels of serum IgG against type VII collagen were significantly lower in mutant compared with wild-type mice. Analysis of serum levels of specific autoantibodies induced in FcRn-deficient and wild-type mice (n = 10 per group) by immunization with type VII collagen showed significantly lower serum levels of IgG against type VII collagen in FcRn-deficient mice compared with wild-type animals. Importantly, the extent of blistering disease after injection of IgG against type VII collagen was significantly reduced in FcRn-deficient mice compared to wild-type controls. Our data demonstrate that FcRn maintains levels of pathogenic autoantibodies and thereby promotes tissue injury in experimental EBA. Therefore, modulation of FcRn function using inhibitors may reduce pathogenic IgG levels, offering therapeutic benefit in patients with antibody-mediated diseases.
Sesarman
Alina
A
Department of Dermatology, University of Lübeck, Lübeck, Germany.
Sitaru
Ana Gabriela
AG
Olaru
Florina
F
Zillikens
Detlef
D
Sitaru
Cassian
C
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D024143:Collagen Type VII / Q000276:immunology; D016107:Epidermolysis Bullosa Acquisita / Q000276:immunology* / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D011961:Receptors, Fc / Q000172:deficiency / Q000235:genetics* / Q000276:immunology
D001323:Autoantibodies; D024143:Collagen Type VII; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal