Dupilumab, approved for moderate-to-severe atopic dermatitis, works by blocking which receptor signalling pathway?
- A IgE receptor (FcεRI) on mast cells and basophils
- B IL-4Rα, thereby blocking both IL-4 and IL-13 signalling ✓
- C IL-31Rα selectively blocking IL-31 (pruritic cytokine)
- D JAK1/JAK2 intracellular kinases non-selectively
Correct answer: B. IL-4Rα, thereby blocking both IL-4 and IL-13 signalling
Explanation
Dupilumab is a human monoclonal antibody against the IL-4 receptor alpha (IL-4Rα) subunit, shared by both the type I (IL-4Rα/γc) and type II (IL-4Rα/IL-13Rα1) receptor complexes. This dual blockade inhibits signalling of both IL-4 and IL-13, the principal Th2 cytokines driving type 2 inflammation in atopic dermatitis. Nemolizumab targets IL-31Rα; omalizumab targets IgE; abrocitinib/upadacitinib are JAK inhibitors.
Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.
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