Deciphering Sjögren's disease: New insights and perspectives extend from advanced omics approaches and immunology

Sjögren's disease (SjD), formerly termed Sjögren's syndrome, is a chronic autoimmune exocrinopathy that has seen substantial advances in basic research over the past decade. Classical experimental approaches have revealed immune dysregulation encompassing aberrant activation of the adaptive immune system, activation of humoral autoimmunity against autoantigens, and upstream participation of innate immune mechanisms. In parallel, with the rapid development of sequencing and omics technologies, researchers are able to use these high-throughput methods to gain a more unbiased, sytem-wide view of disease processes and pathegenesis in SjD. Among them, numerous disease-associated traits have been revealed by genomics and epigenomics, while transcriptomics, proteomics, and immunogenomics have also depicted a more detailed landscape of phenotypes and cell states of immune cells, as well as the roles of key molecules such as Toll-like receptors (TLRs) in promoting autoimmune responses, yielding profound insights for the understanding of SjD. Meanwhile, these diverse data analysis methods offer the researchers impotant tools to further invertigate and understand SjD in the future. The convergence of these modalities supports data-driven disease prediction, refined patient stratification, and identification of therapeutic targets, thereby expanding translational opportunities. Collectively, integrating innovative omics with classical methodologies provides a coherent framework for capturing the pathogenesis of SjD, linking system-wide views to experimental validation, and accelerating the path from pathobiology to precision therapeutics. This review summarizes recent advances in the understanding of the pathogenesis of SjD, lymphomagenesis in SjD, patient stratification and promising targeted therapy, and also outlines future perspectives and challenges to be addressed.