Which mechanism best explains the pathogenesis of intraepidermal blistering with acantholysis and preservation of the basal layer in pemphigus vulgaris?

Which mechanism best explains the pathogenesis of intraepidermal blistering with acantholysis and preservation of the basal layer in pemphigus vulgaris?

• A. Immediate (type I) hypersensitivity reaction to a topically applied agent
• B. Infection with a herpesvirus
• C. Development of autoantibodies against desmosomal proteins
• D. Deposition of IgA-containing immune complexes within dermal papillae

Answer: (C)

Autoantibody-mediated disruption of desmosomes in the epidermis is the key mechanism. In pemphigus vulgaris, IgG autoantibodies bind desmoglein proteins (desmoglein 3, and sometimes desmoglein 1) that hold keratinocytes together. This interference causes loss of cell–cell adhesion between keratinocytes (acantholysis), producing intraepidermal blisters. The basal layer remains attached to the basement membrane via hemidesmosomes, so the bottom layer of cells is preserved, giving a tombstone appearance on microscopy. Immunofluorescence shows an intercellular (fishnet) pattern of IgG throughout the epidermis, consistent with antibody targeting desmosomal components.

Autoantibody-mediated disruption of desmosomes in the epidermis is the key mechanism. In pemphigus vulgaris, IgG autoantibodies bind desmoglein proteins (desmoglein 3, and sometimes desmoglein 1) that hold keratinocytes together. This interference causes loss of cell–cell adhesion between keratinocytes (acantholysis), producing intraepidermal blisters. The basal layer remains attached to the basement membrane via hemidesmosomes, so the bottom layer of cells is preserved, giving a tombstone appearance on microscopy. Immunofluorescence shows an intercellular (fishnet) pattern of IgG throughout the epidermis, consistent with antibody targeting desmosomal components.