Multi-omics in systemic sclerosis with emphasis on extracellular vesicles

Abstract Systemic sclerosis (SSc) is a rare and complex autoimmune disease of unknown aetiology. Although vasculopathy, immune dysregulation, and fibrosis are recognized as key features of the disease, the mechanisms and factors driving their onset and progression remain incompletely understood. In recent years, advances in omics technologies including genomics, epigenomics, transcriptomics, proteomics, and metabolomics have facilitated the identification of dysregulated molecular pathways and potential biomarkers, providing deeper insights into SSc pathophysiology. In this review, we first discuss the results of omics studies in plasma and in specific organs, particularly the lungs and skin, which are the organs primarily affected by SSc. The role of the identified molecules is discussed in relation to the various dysregulated pathways in the disease. We then focus on omics studies of extracellular vesicles (EVs). Despite the limited number of studies, the systemic nature of SSc makes it crucial to determine whether EVs can transport molecular components, including small non-coding RNAs, proteins and metabolites, that contribute to disease exacerbation. The omics data provide valuable information about the molecules that are transported by EVs and the underlying mechanisms that drive disease progression, potentially enabling the discovery of new biomarkers for improved diagnosis and prognosis. We also discuss the advantages of using EVs rather than conventional biomarkers in SSc, as well as the challenges and recommendations for omics analysis.