Why human pemphigoid autoantibodies do not trigger disease by the passive transfer into mice?
The recapitulation of disease features in animals by the transfer of patient autoantibodies has been used to demonstrate the autoimmune nature of several diseases. Failure of disease induction by the passive transfer of autoantibodies has been assigned to a limited cross-reactivity of the autoantibodies with the murine tissue. However, the possibility that the passively transferred "inflammatory" patient autoantibodies may not be able to unfold their pathogenic potential due to restricted Fc-dependent effector functions has not yet been systematically explored. In this study we analyze the interaction of patients' autoantibodies with murine complement and granulocytes. Bullous pemphigoid is a blistering disease associated with autoantibodies, which are thought to induce subepidermal blistering by activating complement and granulocytes. The passive transfer of patients autoantibodies failed to induce skin blistering in wild type mice. The cross-reactivity of pemphigoid autoantibodies with murine antigens was analyzed in silico, ex vivo and by the passive transfer of IgG in vivo. Complement-fixing ability of patients' autoantibodies was evaluated by complement-binding test. Granulocyte activation was assessed by reactive oxygen species production assay and the cryosection model. We have found that although pemphigoid autoantibodies bound to murine skin in vitro and in vivo, they showed a lower capacity to fix murine complement and a reduced ability to activate murine granulocytes when compared with human complement and cells, respectively. These results indicate that for disease models using the passive transfer of patient autoantibodies, their interaction with the innate factors of the host should be optimized to match the human situation.
Department of Dermatology, University of Freiburg, Freiburg, Germany.
Alina
A
Sesarman
Eva
E
Oswald
Mircea T
MT
Chiriac
Kinga
K
Csorba
Vlad
V
Vuta
Vasile
V
Feldrihan
Adrian
A
Baican
Leena
L
Bruckner-Tuderman
Cassian
C
Sitaru
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D010391:Pemphigoid, Bullous / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D046509:Tissue Culture Techniques
D001323:Autoantibodies; D007074:Immunoglobulin G; D017382:Reactive Oxygen Species