Autoantibodies against cell adhesion molecules in pemphigus

Area of Science:

• Molecular biology
• Immunology
• Dermatology

Background:

• Pemphigus vulgaris (PV) and pemphigus foliaceus are autoimmune blistering diseases.
• Autoantigens in these diseases belong to the desmoglein subfamily of cadherins.

Purpose of the Study:

• To understand the pathophysiology of pemphigus using molecular engineering.
• To identify pathogenic epitopes on pemphigus vulgaris antigen (PVA).
• To develop a therapeutic agent targeting pathogenic autoantibodies.

Main Methods:

• cDNA cloning of pemphigus autoantigens.
• Molecular engineering of chimeric molecules and bacterial fusion proteins.
• Baculovirus expression of secreted recombinant PVA (PVIg).
• Immunoabsorption assays and neonatal mouse models.

Main Results:

• The extracellular domain of PVA mediates homophilic cell adhesion.
• Major immunogenic domains of PVA are EC1, EC2, and EC4.
• A pathogenic epitope is located on the amino-terminal region of PVA.
• PVIg absorbed pathogenic autoantibodies and prevented blister formation in mice.

Conclusions:

• The extracellular domain of PVA is crucial for cell adhesion and contains pathogenic epitopes.
• Recombinant PVIg shows therapeutic potential by neutralizing autoantibodies in pemphigus.