Molecular Hydrogen Ameliorates Anti-Desmoglein 1 Antibody-Induced Pemphigus-Associated Interstitial Lung Disease by Inhibiting Oxidative Stress

TL;DR

Molecular hydrogen reduces lung damage in a mouse model of pemphigus-related lung disease by fighting oxidative stress.

Contribution

This study identifies anti-Dsg 1 antibodies as key drivers of lung disease and demonstrates molecular hydrogen's therapeutic potential.

Findings

Anti-Dsg 1 antibodies induce interstitial lung inflammation and fibrosis in mice.

Molecular hydrogen reduces oxidative stress and prevents lung fibrosis in the disease model.

Hydrogen treatment restores antioxidant balance and attenuates lung injury.

Abstract

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.

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