Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients.
Epidermolysis bullosa acquisita (EBA) is an autoimmune sub-epidermal blistering disease characterized by autoantibodies to type VII (anchoring fibril) collagen. To date, however, direct evidence for a pathogenic role of human EBA autoantibodies has not been demonstrated. In this study, we affinity-purified anti-type VII collagen antibodies from EBA patients' sera and then injected them into adult hairless immunocompetent mice. Mice injected with EBA autoantibodies developed skin fragility, blisters, erosions, and nail loss on their paws - all features of EBA patients. By clinical, histological, immunological, and ultrastructural parameters, the induced lesions were reminiscent of human EBA. Histology showed bullous lesions with an epidermal-dermal separation. IgG and C3 deposits were observed at the epidermal-dermal junction. All mice had serum antibodies that labeled the dermal side of salt-split human skin like EBA sera. Direct immunogold electron microscopy specifically localized deposits of human IgG to anchoring fibrils. (Fab')(2) fragments generated from EBA autoantibodies did not induce disease. We conclude that EBA human patient autoantibodies cause sub-epidermal blisters and induce EBA skin lesions in mice. These passive transfer studies demonstrate that human EBA autoantibodies are pathogenic. This novel EBA mouse model can be used to further investigate EBA autoimmunity and to develop possible therapies.
Department of Dermatology, The Keck School of Medicine at the University of Southern California, Los Angeles, California, USA. dwoodley@usc.edu
David T
DT
Woodley
Ramin
R
Ram
Arvin
A
Doostan
Pubali
P
Bandyopadhyay
Yi
Y
Huang
Jennifer
J
Remington
Yingping
Y
Hou
Douglas R
DR
Keene
Zhi
Z
Liu
Mei
M
Chen
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D024143:Collagen Type VII / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D051379:Mice / Q000276:immunology*; D016253:Microscopy, Immunoelectron; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure
D001323:Autoantibodies; D024143:Collagen Type VII; D003176:Complement C3; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G