What's new in bullous pemphigoid

Area of Science:

• Immunodermatology
• Autoimmune Blistering Diseases
• Molecular Mechanisms of Skin Disease

Background:

• Bullous pemphigoid (BP) is the most prevalent autoimmune blistering disease.
• Pathogenesis involves autoantibodies against type XVII collagen (COL17), specifically its NC16A domain.
• Previous models failed to induce blisters with human BP IgG due to species-specific epitope differences.

Purpose of the Study:

• To investigate the pathogenicity of human anti-COL17 IgG autoantibodies in a relevant in vivo model.
• To elucidate the role of COL17 in BP-induced dermal-epidermal separation.

Main Methods:

• Utilized COL17-humanized mice expressing human COL17 but lacking murine COL17.
• Administered IgG autoantibodies from BP patients to these humanized mice.
• Monitored for immune reactions and dermal-epidermal separation.

Main Results:

• Passive transfer of human BP IgG induced immune reactions, including complement activation, mast cell degranulation, and neutrophilic infiltration in humanized mice.
• Demonstrated dermal-epidermal separation, confirming the pathogenicity of human anti-COL17 IgG autoantibodies in vivo.
• Established a functional model for studying BP pathogenesis.

Conclusions:

• Human anti-COL17 IgG autoantibodies are pathogenic in vivo, causing blistering in the context of human COL17.
• COL17-humanized mice represent a breakthrough model for BP research.
• Findings pave the way for developing targeted and effective BP therapies.