The filaggrin (FLG) gene mutations found in atopic dermatitis (AD) patients affect epidermal barrier function. Which of the following best describes the downstream consequence of filaggrin deficiency that perpetuates the AD inflammatory cycle?
- A Deficient melanin production leading to skin lightening
- B Impaired keratinocyte cornification leading to blisters
- C Increased transepidermal water loss (TEWL), reduced natural moisturising factors (NMFs), and enhanced allergen penetration triggering Th2-skewed immune response ✓
- D Reduced antimicrobial peptide production allowing S. aureus colonisation alone
Explanation
Filaggrin is a structural protein that aggregates keratin filaments in the cornified envelope and is proteolytically processed into natural moisturising factors (amino acids, urocanic acid, pyrrolidone carboxylic acid) that maintain stratum corneum hydration. FLG null mutations cause: deficient NMF synthesis, increased TEWL (impaired water retention), disturbed SC lipid organisation, elevated SC pH, and enhanced percutaneous penetration of allergens/irritants/microbes. This activates keratinocyte TSLP, IL-25, and IL-33 release, driving Th2 polarisation and IgE sensitisation — the outside-in hypothesis of AD pathogenesis.
Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.