Pathogenic human monoclonal antibody against desmoglein 3

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Pemphigus vulgaris (PV) is a severe autoimmune disease.
• It involves IgG autoantibodies targeting desmoglein 3 (Dsg3).
• Dsg3 is crucial for epidermal keratinocyte adhesion.

Purpose of the Study:

• To characterize a novel human monoclonal antibody, PVMAB786.
• To investigate its potential as a research tool for PV.

Main Methods:

• Isolation of PVMAB786 from an untreated PV patient.
• Testing antibody reactivity against keratinocytes and recombinant Dsg3.
• Inducing acantholysis in human tissues and a mouse model.

Main Results:

• PVMAB786 is a Dsg3-specific IgG4 antibody.
• It binds to Dsg3 on keratinocytes and recombinant Dsg3, not Dsg1.
• The antibody induced acantholysis and mimicked PV in mice.

Conclusions:

• PVMAB786 is a valuable tool for studying Dsg3's role in PV.
• It aids research into epithelial cell adhesion and acantholysis mechanisms.
• Further research can explore Dsg3 processing, presentation, and V gene/isotype usage in PV.