A patient presents with a blistering skin disorder; direct immunofluorescence shows IgG on keratinocytes. Which cell–cell junction is most likely involved?

• A. Hemidesmosomes
• B. Tight junctions
• C. Adherens junctions
• D. Desmosomes

Answer: (D)

Autoimmune blistering diseases can reveal exactly which adhesion structures are being attacked by where the antibodies deposit. When direct immunofluorescence shows IgG decorating keratinocytes in an intercellular pattern, it points to antibodies against desmosomal proteins that hold adjacent keratinocytes together. Desmosomes are the cell–cell junctions in the epidermis that provide strong adhesion between neighboring keratinocytes; their disruption causes acantholysis and intraepidermal blisters. This pattern fits pemphigus vulgaris, where autoantibodies target desmogleins, weakening cell–cell cohesion within the epidermis. If the antibodies were against basement membrane components, you’d see linear IgG at the dermal–epidermal junction and subepidermal blisters, implicating hemidesmosomes instead.