Pemphigus-associated interstitial lung disease (P-ILD) is a severe complication observed in pemphigus patients that is characterized by pulmonary interstitial inflammation and fibrosis. This study investigated the role of anti-desmoglein (Dsg) 1/3 antibodies in P-ILD pathogenesis and evaluated the therapeutic potential of molecular hydrogen (H2). Using a BALB/cJGpt mouse model, we demonstrated that anti-Dsg 1 antibodies, but not anti-Dsg 3 antibodies, induced interstitial inflammation and fibrosis. Immunofluorescence staining confirmed IgG deposition in the alveolar epithelium, suggesting immune complex formation and epithelial damage. Gene expression analysis revealed elevated pro-inflammatory cytokines (IL-1β, IL-13) and upregulated pro-fibrotic markers (α-SMA, S100A4, TGF-β, and collagen genes) in P-ILD progression. Elevated oxidative stress and impaired ROS metabolism further implied the role of oxidative damage in disease pathogenesis. To assess H2‘s therapeutic potential, hydrogen-rich water was administered to P-ILD mice. H2 treatment significantly reduced oxidative stress, attenuated interstitial inflammation, and prevented pulmonary fibrosis. These protective effects were attributed to H2‘s antioxidant properties, which restored the pro-oxidant-antioxidant balance. Our findings underscore the critical role of anti-Dsg 1 antibodies and oxidative stress in P-ILD and highlight H2 as a promising therapeutic agent for mitigating anti-Dsg 1 antibody-induced lung injury.
Tang C, Wang L, Chen Z, et al. Molecular Hydrogen Ameliorates Anti-Desmoglein 1 Antibody-Induced Pemphigus-Associated Interstitial Lung Disease by Inhibiting Oxidative Stress. Int J Mol Sci. 2025;26(9):4203.