Pathogenesis of interstitial lung disease in systemic sclerosis

Area of Science:

• Rheumatology and Immunology
• Pulmonary Medicine
• Genetics

Background:

• Interstitial lung disease (ILD) is a major complication of systemic sclerosis (SSc), significantly impacting patient morbidity and mortality.
• The pathogenesis of SSc-ILD is closely linked to the underlying factors driving SSc, involving complex genetic and immunological elements.
• Understanding SSc-ILD susceptibility is crucial, as it exhibits variability influenced by genetic architecture, including immunogenomic and non-immunological factors.

Purpose of the Study:

• To elucidate the pathogenic mechanisms underlying SSc-ILD.
• To identify genetic factors contributing to SSc-ILD susceptibility and geographical/racial diversity.
• To explore the links between autoantibody subgroups, genetic predispositions, and SSc-ILD risk.

Main Methods:

• Analysis of blood and tissue samples from patients.
• Conducting observational clinical research.
• Integrated analysis of in vitro and in vivo preclinical models.
• Examination of clinical trial cohorts and high-dimensional bio-sample analysis.

Main Results:

• Confirmed the critical role of immune mechanisms (innate and adaptive) in SSc-ILD.
• Highlighted the significant involvement of profibrotic pathways, particularly transforming growth factor beta (TGF-beta) and its regulators.
• Identified genetic associations contributing to SSc-ILD susceptibility and diversity.

Conclusions:

• Pathogenic mechanisms of SSc-ILD involve intricate immune responses and profibrotic signaling.
• Genetic factors play a substantial role in SSc-ILD susceptibility and its diverse clinical manifestations.
• Further research into these mechanisms will advance stratified and precision medicine approaches for SSc-ILD treatment.