Molecular classification of primary Sjögren’s syndrome based on salivary gland omics

Primary Sjögren’s syndrome is a complex and heterogeneous disease, often involving multiple organ systems and carrying an increased risk of lymphoma development. In this study, we integrated single-cell RNA sequencing and bulk RNA-seq data to deconvolute the disease heterogeneity using non-negative matrix factorization.This analysis identified four distinct molecular subtypes, which we designated as the Classical Immune Type, Ion Channel Type, Fibrotic Senescent Type, and Immune Desert Type. Through differential expression analysis, we further identified characteristic gene sets for each of these subtypes. The Gene Set Variation Analysis scores of these subtype-specific gene signatures in patient minor salivary gland RNA-seq data may potentially inform patient stratification. We preliminarily characterized the clinical features and local immune microenvironment profiles associated with each subtype. These findings may have implications for personalized therapeutic strategies and potentially inform the selection of patients for future clinical trials.