Dissecting the Heterogeneity of Skin Gene Expression Patterns in Systemic Sclerosis

The study examined skin gene expression in systemic sclerosis (SSc) using samples from 61 SSc patients and 36 controls. Researchers identified 2,754 differentially expressed transcripts, revealing two main transcriptomes: keratin and fibroinflammatory signatures. The keratin signature was linked to shorter disease duration and interstitial lung disease, while the fibroinflammatory signature correlated with diffuse cutaneous involvement and higher skin scores. A subgroup with longer disease duration showed a normal-like transcript pattern. There was notable heterogeneity in cell type-specific signatures, with elevated scores for fibroblasts, microvascular cells, macrophages, and dendritic cells. The keratin signature was associated with activation in hair and adnexal structures, not general keratinocyte activation. These findings highlighted the heterogeneity in SSc skin, suggesting potential for patient stratification in targeted therapies or predicting immunosuppression response.