Track: Basic Science

Abstract:

Background:
Bullous pemphigoid (BP) is an autoimmune blistering disorder. Autophagy is a regulated lysosomal degradation pathway essential for epidermal homeostasis, keratinocyte differentiation, stress adaptation, and immune modulation. Keratinocytes treated with IgG from BP patients (BP-IgG) have been shown to develop marked morphological accumulation of autophagosomes and lysosomes. However, the role of autophagy in the epidermis of bullous pemphigoid remains unclear.
Methods:
Skin biopsies from BP, Spongiotic dermatitis (SD), and normal skin (NL) were stained for LC3B and p62 by immunohistochemistry (IHC). Cytoplasmic and nuclear staining intensities were quantified. LC3B marks autophagosome formation, while p62 is degraded during autophagy. Statistical analysis was performed using the Mann–Whitney U test. For in vitro analysis, immortalized human keratinocytes (nTERT) were treated with affinity purified BP-IgG or IgG from healthy control for 2 hours. Immunocytochemistry (ICC) for LC3B was subsequently performed.
Results:
BP skin exhibited significantly increased LC3B expression (P = 0.04) and a trend towards decrease p62 (P = 0.010) compared to NL, particularly with nuclear LC3B significantly higher in BP (p = 0.0445). Autophagy scores were overall elevated in BP. SD showed similar trends to BP. In vitro, BP-IgG treated nTERT cells exhibited increased LC3 fluorescence intensity compared to control IgG (P=0.0027).
Conclusions:
BP is associated with an epidermal autophagy signature characterized by increased LC3B and reduced p62. In vitro findings indicate that BP autoantibodies can directly induce autophagy in keratinocytes. These results support autophagy as both a marker of keratinocyte stress and a potential therapeutic target in BP.