Skin transcriptomic profiles may be used to potentially identify patients with systemic sclerosis (SSc) who are at risk of interstitial lung disease (ILD), according to a poster presentation at the ERS International Congress 2023 in Milan, Italy. 

SSc is a connective tissue disease that is most often characterized by skin fibrosis and fibrosis of the internal organs, accompanied by impaired immunity. Patients with this disorder may develop interstitial lung disease, a condition that affects over half of patients with SSc. Lung disease in SSc remains one of the leading causes of disease-specific mortality. 

Nevertheless, it is clinically challenging to predict whether a patient with SSc will go on to develop ILD. This means that treatment is often delayed, and there is a lack of consensus regarding the efficacy of therapeutics used to treat ILD associated with SSc. 

Zielonka and colleagues hypothesized that skin transcriptomes may be useful as an intermediate phenotype to assess lung function impairment. This method also has a considerable advantage as it is noninvasive. 

Read more about SSc etiology 

The research team accessed the Gene Express Omnibus and selected 2 databases. They used weighted gene correlation analysis to identify clusters of highly correlated genes (modules); they then identified modules that had significant overlap between databases and performed pathway analysis. 

In the first database, the researchers identified 13 modules that correlated with skin score; in the second database, they identified 7 modules that correlated with skin score and lung function. In total, 10 groups of overlapping modules were identified. The research team then performed pathway analysis, including cytokine-cytokine receptor interaction, extracellular matrix receptor interaction, and the signaling of chemokines. 

The research team reported that skin transcriptomic profiles of 2 distinct databases were able to yield a number of gene networks associated with skin and lung function severity involvement in SSc. 

“These non-invasive signatures have the potential to identify patients at risk of lung disease and may define pathways for novel pharmacologic targets,” they concluded. 


Zielonka J, Li N, Wang Z, Yan X, Gomez J. Skin transcriptomes link severity of skin involvement and lung function impairment in systemic sclerosis. Poster presented at: European Respiratory Society International Congress, Milan, Italy; Sept. 9-13, 2023. Poster OA856.