Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology

Area of Science:

• Dermatology
• Immunology
• Cell Biology

Background:

• Pemphigus pathogenesis is debated, with differing theories on intra-epidermal blistering.
• Understanding the role of desmogleins (Dsgs) and other factors is crucial for pemphigus etiology.

Purpose of the Study:

• To highlight and compare the monopathogenic and multipathogenic theories of pemphigus pathogenesis.
• To discuss the implications of desmoglein compensation and multiple hit hypotheses.
• To identify future research directions in pemphigus pathophysiology.

Main Methods:

• This is a viewpoint article, presenting a theoretical discussion.
• It analyzes existing hypotheses regarding pemphigus blistering mechanisms.

Main Results:

• The monopathogenic theory posits that desmoglein (Dsg) antibody-mediated keratinocyte (KC) adhesion disruption causes blistering.
• The multipathogenic theory suggests that multiple factors, including partnering autoantibodies, are needed for irreversible KC damage and blistering.
• Single autoantibodies may induce reversible changes, necessitating additional insults for disease progression.

Conclusions:

• The contribution of non-desmoglein (Dsg) specific autoantibodies to pemphigus pathophysiology requires further investigation.
• Future studies should corroborate findings and characterize patient populations with non-Dsg antibodies.
• Clarifying the interplay of various pathogenic factors is essential for a comprehensive understanding of pemphigus.