Immune response in pemphigus and beyond: progresses and emerging concepts

Area of Science:

• Immunodermatology
• Autoimmune Bullous Diseases
• Cell Adhesion Biology

Background:

• Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are severe autoimmune blistering diseases.
• Autoantibodies against desmoglein (Dsg) 1 and/or Dsg3 are key pathogenic factors.
• Desmogleins are crucial for cell adhesion in stratified epithelia.

Purpose of the Study:

• To review advances in understanding the immune response in pemphigus.
• To explore genetic susceptibility, pathogenic antibodies, and cellular players.
• To discuss the implications for pemphigus management and therapy.

Main Methods:

• Review of current literature on pemphigus pathogenesis.
• Analysis of genetic associations (HLA class II).
• Characterization of anti-Dsg antibodies and Dsg-specific immune cells.
• Examination of passive and adoptive transfer models in mice.

Main Results:

• Pathogenicity of anti-Dsg autoantibodies is well-established.
• Disease activity correlates with antibody titers and profiles.
• Animal models successfully recapitulate pemphigus phenotypes.
• Intracellular signaling is implicated in cell-cell dissociation in PV.

Conclusions:

• Desmogleins play a critical role in epithelial tissue homeostasis.
• Understanding pemphigus pathogenesis is advancing rapidly.
• New insights pave the way for targeted immunologic and pharmacologic therapies for pemphigus.