In pemphigus vulgaris, the histopathological hallmark is acantholysis above the basal layer. Which of the following best describes the mechanism by which anti-desmoglein-3 antibodies cause acantholysis?
- A Complement-mediated lysis of keratinocytes
- B Steric hindrance of desmoglein adhesion and intracellular signaling leading to plakoglobin nuclear translocation and p38 MAPK activation ✓
- C T-cell-mediated cytotoxicity against basal keratinocytes
- D Blocking of hemidesmosomal BP180 leading to subepidermal cleavage
Correct answer: B. Steric hindrance of desmoglein adhesion and intracellular signaling leading to plakoglobin nuclear translocation and p38 MAPK activation
Explanation
Acantholysis in pemphigus is not purely steric. Anti-Dsg3 IgG causes both steric inhibition of Dsg3 trans-interaction and activates intracellular signaling: nuclear translocation of plakoglobin suppresses Dsg3 expression, while p38 MAPK activation leads to cytoskeletal collapse and Dsg3 internalization. Complement is not essential. Hemidesmosomes are targeted in pemphigoid, not pemphigus.
Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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