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Article Abstract
Introduction: Sjögren's syndrome (SS) is an autoimmune disorder affecting exocrine glands, causing dry mouth and eyes, with no effective treatment. While high-throughput sequencing has provided insights into its mechanisms, the role of alternative splicing (AS) in SS remains underexplored.
Objective: To investigate the relationship between immune infiltration in the salivary glands and AS events at the transcriptomic level, and to identify potential biomarkers that may be linked to the diagnosis and prognosis of SS.
Methods: Transcriptomic data from salivary glands were aligned to the GRCh38 genome using HISAT2. Isoform quantification was performed with StringTie, and differential isoform usage was analyzed with DEXSeq in the IsoformSwitchAnalyzeR pipeline. Further analyses were conducted to explore the relationship between AS events, clinical data and immune infiltration.
Results: 16 genes showed significant alternative splicing between biopsy-positive and biopsy-negative salivary glands. These genes were linked to immune regulation. Isoform usage ratios integrated with clinical data identified MAP4K1, SH2D3C, and ACAP1 isoforms as potential diagnostic biomarkers. Immune infiltration analysis showed a strong correlation between memory B cells, follicular helper T cells, and biopsy scores, with significant differences between biopsy-positive and biopsy-negative tissues. A correlation between immune infiltration and isoform usage provided insights into gene function and disease progression.
Conclusions: This study reveals the critical role of AS in SS, identifying 16 genes with differential isoform usage that may serve as biomarkers for diagnosis and prognosis. The link between immune infiltration and splicing suggests that AS influences immune responses in SS, providing opportunities for targeted therapies. These findings emphasize AS's importance in SS and offer new diagnostic and therapeutic avenues.
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| http://dx.doi.org/10.1007/s13258-025-01633-y | DOI Listing |
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