Multi-omic analysis identifies biological processes underlying progressive interstitial lung disease in systemic...

Area of Science:

• Autoimmune diseases
• Connective tissue disorders
• Pulmonary medicine

Background:

• Systemic sclerosis (SSc) is a rare autoimmune disorder.
• Interstitial lung disease (ILD) is the main cause of mortality in SSc patients.
• Identifying biomarkers for ILD progression in SSc is crucial.

Purpose of the Study:

• To identify markers associated with ILD progression in SSc patients.
• To compare biological profiles of SSc patients with and without ILD.
• To investigate the multi-level biological picture of SSc-related ILD.

Main Methods:

• Analysis of plasma, whole blood, and skin biopsies from 52 SSc patients and 5 healthy volunteers.
• Utilized metabolomics, proteomics, cytokine quantification, gene expression profiling, and immunophenotyping.
• Compared patients with progressive ILD, no ILD, and healthy volunteers.

Main Results:

• Elevated pro-inflammatory markers (interferon-1, fractalkine, CCL2) and profibrotic markers (CXCL17, thrombospondin, LTBP1) were found in SSc-ILD.
• Lower cellular inflammatory activity observed in SSc-ILD patients, possibly due to immunosuppressive therapies.
• ILD progression correlated with increased plasma levels of cytoskeletal proteins and triglycerides.

Conclusions:

• Pro-inflammatory and profibrotic mechanisms are involved in SSc-related ILD.
• Elevated triglyceride levels represent a novel potential biomarker for ILD progression in SSc.
• Triglycerides may contribute to fibrogenesis through endoplasmic reticulum stress.