Involvement of Ferroptosis in Bullous Pemphigoid Pathogenesis

Area of Science:

• Cellular biology
• Immunodermatology
• Pathophysiology

Background:

• Bullous pemphigoid (BP) predominantly affects the elderly and is often associated with conditions linked to ferroptosis.
• The specific role of ferroptosis in the pathogenesis and prognosis of bullous pemphigoid remains largely unexplored.

Purpose of the Study:

• To investigate the involvement of ferroptosis in the development of bullous pemphigoid.
• To assess the impact of ferroptosis on the prognosis of bullous pemphigoid.

Main Methods:

• Analysis of ferroptosis-related gene expression in BP lesions using single-cell and bulk RNA sequencing.
• Validation of mRNA and protein expression of ferroptosis markers in skin lesions via qRT-PCR, immunofluorescence, and Western blot.
• In vitro studies using HaCaT cells stimulated with BP blister fluid to confirm ferroptosis involvement, alongside ELISA for serum biomarkers.

Main Results:

• Abnormal expression of ferroptosis genes (e.g., decreased GPX4, increased VDAC2/3) observed in BP lesions and in vitro models.
• Elevated serum levels of ferritin, transferrin, and pro-inflammatory cytokines (HMGB1, IL-5, IL-6, IL-18, IL-31, IL-1β) in BP patients, which decreased post-treatment.
• BP blister fluid promoted cytokine production and increased iron, Fe2+, and ROS levels in vitro; serum ferritin correlated with disease severity (BPDAI) and inflammatory markers (anti-180 antibody, CRP).

Conclusions:

• Ferroptosis is a significant factor in the pathophysiology of bullous pemphigoid.
• Ferroptosis markers may serve as predictive indicators for bullous pemphigoid prognosis.
• Targeting ferroptosis presents a potential therapeutic avenue for bullous pemphigoid treatment.