The role of complement in experimental bullous pemphigoid.
Bullous pemphigoid (BP) is a blistering skin disease associated with an IgG autoimmune response directed against the ectodomain of the hemidesmosomal protein, BP180. An animal model of BP has recently been developed by our laboratory based on the passive transfer of rabbit antimurine BP180 antibodies into neonatal BALB/c mice. The experimental animals develop a blistering disease that reproduces all of the key immunopathological features of BP. In the present study we have investigated the role of complement in the pathogenesis of subepidermal blistering in the mouse model of BP. We demonstrate the following. (a) Rabbit anti-murine-BP180 IgG was effective in inducing cutaneous blisters in a C5-sufficient mouse strain, but failed to induce disease in the syngeneic C5-deficient strain; (b) neonatal BALB/c mice, pretreated with cobra venom factor to deplete complement, became resistant to the pathogenic effects of the anti-BP180 IgG; (c) F(ab')2 fragments generated from the anti-BP180 IgG exhibited no pathogenic activity in the mouse model; and (d) histologic evaluation of the skin of mice described in points b and c above showed minimal or no neutrophilic cell infiltration in the upper dermis. Thus, anti-BP180 antibodies trigger subepidermal blistering in this BP model via complement activation. This experimental model of BP should greatly facilitate future studies on the pathophysiology of autoantibody-mediated diseases of the dermal-epidermal junction.
Liu
Z
Z
Department of Dermatology, Medical College of Wisconsin, Milwaukee 53226, USA.
Giudice
G J
GJ
Swartz
S J
SJ
Fairley
J A
JA
Till
G O
GO
Troy
J L
JL
Diaz
L A
LA
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001768:Blister / Q000209:etiology; D003167:Complement Activation; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000209:etiology* / Q000276:immunology*; D012867:Skin / Q000473:pathology; D000097805:Collagen Type XVII
D001324:Autoantigens; D003182:Complement C5; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII