Association of differentially expressed genes and autoantibody type in patients with systemic sclerosis

Objectives The aims of this study were to investigate the relationship between the type of autoantibody and gene expression profile in skin lesions from patients with SSc, and to identify specific dysregulated pathways in SSc patients compared with healthy controls. Methods Sixty-one patients with SSc from the Genetics vs Environment in Scleroderma Outcome Study cohort and 36 healthy controls were included in this study. Differentially expressed genes were extracted and functional enrichment and pathway analysis were conducted. Results Compared with healthy controls, lists containing 2, 71, 10, 144 and 78 differentially expressed genes were created for patients without specific autoantibody, ACA, anti-U1 RNP antibody (RNP), anti-RNA polymerase III antibody (RNAP) and anti-topoisomerase I antibody (ATA), respectively. While part of the enriched pathways overlapped, distinct pathways were identified except in those patients lacking specific autoantibody. The distinct enriched pathways included 'keratinocyte differentiation' for ACA, 'nuclear factor kappa B signalling' and 'cellular response to TGF-beta stimulus' for RNAP, 'interferon alpha/beta signalling' for RNP, and 'cellular response to stress' for ATA. Cell type signature score analysis revealed that macrophages/monocytes, endothelial cells and fibroblasts were associated with ACA, RNAP, ATA and the severity of the SSc skin lesions. Conclusion Pathogenic pathways were identified according to the type of autoantibody by leveraging gene expression data of patients and controls from a multicentre cohort. The current study may promote the search for new therapeutic targets for SSc.

Automated summary

This study investigated the relationship between different types of autoantibodies and gene expression profiles in skin lesions of patients with Systemic Sclerosis (SSc), identifying specific dysregulated pathways associated with each autoantibody type. By analyzing gene expression data, the study revealed potential new therapeutic targets for SSc based on specific autoantibody profiles.