Epithelial Stress, Myeloid Activation, and Genetic Susceptibility in Sjögren's Disease: A Convergent Model

Epithelial Stress, Myeloid Activation, and Genetic Susceptibility in Sjögren's Disease: A Convergent Model. Integrating scRNA-seq, viral array, and CD8 transcriptomics. Analysis date: 31 May 2026. Data sources: GSE272409 (7 pSS + 6 Sicca, 70,441 cells), GSE302883 (3 pSS + 3 HV), GSE77599 (15 pSS + 14 HV viral array), GSE84844 (30 pSS + 30 HV blood), GSE284327 (CD8 scRNA-seq). This preprint presents a convergent model incorporating Epstein-Barr virus (EBV) as the mechanistic thread connecting genetic susceptibility, immune dysfunction, and clinical phenotype in SS. The central hypothesis is that EBV simultaneously disables CD8-mediated control through viral immune evasion mechanisms, hijacks B cell activation through latent proteins (EBNA2, LMP1), and drives the inflammatory loop that sustains disease activity. Without EBV, core phenomena in SS lack a mechanistic framework linking genetic risk to immune pathology.