Characterization of comprehensive dynamic epigenetic changes during human primary Sjögren’s syndrome progression

BACKGROUND: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by reduced exocrine gland (principally the salivary and lacrimal glands) activity caused by chronic lymphocytic infiltration. Although pSS has been closely associated with an increased risk of mucosa-associated lymphoid tissue (MALT) lymphoma, the dynamic epigenetic changes in the gland cells that accompany the pathogenesis are not entirely understood. METHODS: In this study, we harvested tissue samples from the labial gland with (LG_pSS) or without pSS (LG_NC) before MALT development, as well as the parotid gland with tumor tissues (PG_MALT) and paracancerous tissues (PG_NC) of two pSS patients with MALT lymphoma, and conducted RNA-seq and ChIP-seq for tri-methylated histone 3 lysine 4, 9, 27, 36, and 79 (H3K4/9/27/36/79me3). RESULTS: Transcriptome landscapes indicated two outcomes of pSS progression with or without MALT lymphoma represented by distinct populations of differentially expressed genes and their functions. Furthermore, the epigenetic atlas of genome-wide H3K4/9/27/36/79me3 was in different stages for various samples, indicating that the variance of H3K4me3 was the earliest event, followed by selective alterations of H3K9/27/36/79me3. These four epigenetic modifications determine the final outcome of pSS progression. CONCLUSIONS: Our results not only advance the understanding of the dynamics of pSS progression and highlight the importance of epigenetic alterations in regulating transcription during this pathological process, but also identify potential therapeutic targets for pSS treatment and lymphoma intervention.