THE ROLE OF COMPLEMENT IN EXPERIMENTAL BULLOUS PEMPHIGOID

Bullous pemphigoid (BP) is a blistering skin disease associated with a n IgG autoimmune response directed against the ectodomain of the hemid esmosomal protein, BP180. An animal model of BP has recently been deve loped by our laboratory based on the passive transfer of rabbit antimu rine BP180 antibodies into neonatal BALB/c mice, The experimental anim als develop a blistering disease that reproduces all of the key immuno pathological 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 an ti-murine-BP180 IgG was effective in inducing cutaneous blisters in a CS-sufficient mouse strain, but failed to induce disease in the syngen eic C5-deficient strain; (b) neonatal BALB/c mice, pretreated with cob ra venom factor to deplete complement, became resistant to the pathoge nic effects of the anti-BP180 IgG; (c) F(ab')(2) fragments generated f rom the anti-BP180 IgG exhibited no pathogenic activity in the mouse m odel; and (d) histologic evaluation of the skin of mice described in p oints b and c above showed minimal or no neutrophilic cell infiltratio n in the upper dermis, Thus, anti-BP180 antibodies trigger subepiderma l blistering in this BP model via complement activation, This experime ntal model of BP should greatly facilitate future studies on the patho physiology of autoantibody-mediated diseases of the dermal-epidermal j unction.