The role of complement in experimental bullous pemphigoid

Area of Science:

• Immunodermatology
• Autoimmune Blistering Diseases
• Complement System

Background:

• Bullous pemphigoid (BP) is an IgG autoimmune blistering skin disease targeting the hemidesmosomal protein BP180.
• A novel mouse model of BP involves passive transfer of rabbit anti-murine BP180 antibodies into neonatal BALB/c mice.
• This model replicates key immunopathological features of human BP.

Purpose of the Study:

• To investigate the role of the complement system in the pathogenesis of subepidermal blistering within the established mouse model of BP.
• To elucidate the mechanism by which anti-BP180 antibodies induce blistering in this experimental system.

Main Methods:

• Utilized C5-sufficient and C5-deficient mouse strains to assess complement's role.
• Administered cobra venom factor to deplete complement in neonatal BALB/c mice.
• Employed F(ab')2 fragments of anti-BP180 IgG to evaluate antibody-dependent pathogenicity.
• Conducted histological examination of skin biopsies to assess inflammatory cell infiltration.

Main Results:

• Anti-BP180 IgG induced blisters in C5-sufficient mice but not in C5-deficient mice.
• Complement depletion via cobra venom factor rendered mice resistant to anti-BP180 IgG-induced blistering.
• F(ab')2 fragments lacked pathogenic activity, and complement-depleted mice showed minimal neutrophilic infiltration.
• These findings indicate that complement activation is crucial for subepidermal blistering.

Conclusions:

• Anti-BP180 antibodies induce subepidermal blistering in the mouse model of bullous pemphigoid through complement activation.
• This experimental model provides a valuable tool for studying the pathophysiology of autoantibody-mediated diseases affecting the dermal-epidermal junction.
• Complement is a critical mediator in the development of BP.